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Abstract Autophagy-related gene (ATG) 5 regulates blood lipids, chronic inflammation, CD4+ T-cell differentiation, and neuronal death and is involved in post-stroke cognitive impairment. This study aimed to explore the correlation of serum ATG5 with CD4+ T cells and cognition impairment in stroke patients. Peripheral blood was collected from 180 stroke patients for serum ATG5 and T helper (Th) 1, Th2, Th17, and regulatory T (Treg) cell detection via enzyme-linked immunosorbent assays and flow cytometry. The Mini-Mental State Examination (MMSE) scale was completed at enrollment, year (Y)1, Y2, and Y3 in stroke patients. Serum ATG5 was also measured in 50 healthy controls (HCs). Serum ATG5 was elevated in stroke patients compared to HCs (P<0.001) and was positively correlated to Th2 cells (P=0.022), Th17 cells (P<0.001), and Th17/Treg ratio (P<0.001) in stroke patients but not correlated with Th1 cells, Th1/Th2 ratio, or Treg cells (all P>0.050). Serum ATG5 (P=0.037), Th1 cells (P=0.022), Th17 cells (P=0.002), and Th17/Treg ratio (P=0.018) were elevated in stroke patients with MMSE score-identified cognition impairment vs those without cognition impairment, whereas Th2 cells, Th1/Th2 ratio, and Treg cells were not different between them (all P>0.050). Importantly, serum ATG5 was negatively linked with MMSE score at enrollment (P=0.004), Y1 (P=0.002), Y2 (P=0.014), and Y3 (P=0.001); moreover, it was positively related to 2-year (P=0.024) and 3-year (P=0.012) MMSE score decline in stroke patients. Serum ATG5 was positively correlated with Th2 and Th17 cells and estimated cognitive function decline in stroke patients.

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INTRODUCTION: Chronic immune thrombocytopenia (cITP) is characterized by dysregulation of the immune response. Until recently, the role of Th2-related cytokine gene polymorphisms was unclear. Interleukin 4 (IL-4) exerts its functions by binding to three types of IL-4 receptor (IL-4R) complexes. We aimed to explore the potential association between the gene polymorphism of IL-4Rα and cITP. METHODS: We investigated the clinical impact of the IL-4Rα (rs1801275) A>G single nucleotide polymorphism (SNP) using the polymerase chain reaction (PCR) followed by the restriction fragment length polymorphism (RFLP) method in 82 cITP patients and 60 healthy controls (HCs). RESULTS: The IL-4Rα (rs1801275) A>G polymorphism analysis showed the mutant GG genotype was significantly higher in control females (p = 0.033). The wild AA genotype had a higher bleeding score (p = 0.02) in the adulthood onset group. Furthermore, the wild AA genotype in the cITP childhood onset group was significantly associated with the disease severity, as well as the response to treatment (p = 0.040). CONCLUSION: The mutant G allele is protective against the susceptibility to cITP in the Egyptian females. The IL-4Rα (rs1801275) A>G polymorphism may affect the clinical severity of cITP and treatment response in the Egyptian population.

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Diverse immune cell subsets have been described in IgG4-related disease (IgG4-RD). If there is a different immunophenotype according to clinical phenotype and activity status is not known. Levels of IL-4-, IL-13-, IL-5-, and IL-21-producing CD4+ T cells (Th2 subsets), CD4+ cytotoxic T lymphocytes (CD4+CTLs), T helper 9 cells, T follicular helper cells (Tfh; Tfh1/Tfh2/Tfh17/Tf regulatory [Tfr]), Foxp3+ regulatory T cells, Type 1 regulatory T cells (Tr1), T helper 3 regulatory cells (Th3), IL-10-producing regulatory B cells (Bregs), IL-10-expressing regulatory plasmacytoid dendritic (pDC IL-10+) cells, and M1 and M2 monocytes were determined by flow cytometry in 43 IgG4-RD patients and 12 controls. All immune subsets were higher in patients vs. controls. CD4+/IL-4+, CD4+/IL-5+, CD4+CTLs, Tfh2, Tfh17, Tfr, and M1 monocyte cell number was different among IgG4-RD clinical phenotypes. The pancreato-hepato-biliary phenotype was characterized by a higher CD4+CTLs, Tfh17, Tfh2, and Tfr and lower M1 cell number. An increased CD4+CTLs and Th3 cell number distinguished the head and neck-limited phenotype, while the retroperitoneal/aortic and Mikulicz/systemic phenotypes were characterized by increased Th2 subsets. Tfh17, Tr1, Th3, pDC, M1, and M2 monocytes were augmented in active patients. In summary, the clinical heterogeneity of IgG4-RD might be driven by the participation of different immunophenotypes and, consequently, by a different fibroinflammatory process.

Assuntos

Doença Relacionada a Imunoglobulina G4 , Interleucina-10 , Humanos , Interleucina-4 , Interleucina-5 , Fenótipo

RESUMO

BACKGROUND: Patients with biomass exposure-related COPD (BE-COPD) is a prevalent disease in developing countries and requires a detailed study of its clinical and inflammatory characteristics, specifying interventions that may differ from tobacco exposure-related COPD (TE-COPD). The objective was to describe clinical characteristics, biomarkers of inflammation, T-helper cells, and microbiological agents during a COPD exacerbation in BE-COPD in comparison with TE-COPD. METHODS: A prospective observational study in patients with moderate or severe exacerbation was recruited either in the emergency room or the COPD clinic. At enrollment, nasopharyngeal swabs and sputum were collected to identify viral and bacterial pathogens. Blood samples were also collected to measure inflammatory biomarkers and T-helper cells levels. Days of hospitalization and mechanical ventilation requirement was evaluated. RESULTS: Clinical characteristics, vaccination history, hospitalization, history of exacerbations, and microbiological pattern between BE-COPD and TE-COPD were similar. The Th2 profile was higher in BE-COPD than in TE-COPD (2.10 [range 1.30-3.30] vs. 1.40 [range 1.20-1.80], p = 0.001). The Th2/Th1 ratio was higher in BE-COPD than TE-COPD (1.22 [range 0.58-2.57 ] vs. 0.71 [range 0.40-1.15], p = 0.004). The need of mechanical ventilation (MV) was higher in TE-COPD than BE-COPD (13% vs. 31.1%, p = 0.01). Nonvaccination history and high CRP levels were significantly associated with hospitalization [OR 1.48 (CI 95% 1.30-4.61, p = 0.005) and OR 1.17 (CI 95% 1.10-1.24, p = 0.001), respectively]. CONCLUSIONS: Clinical characteristics, inflammatory markers, and microbiological isolates were similar in both groups but BE-COPD show a tendency to present higher inflammatory Th2 cells and low requirement MV compared with TE-COPD.

Assuntos

Asma , Doença Pulmonar Obstrutiva Crônica , Humanos , Nicotiana , Biomassa , Escarro/microbiologia , Biomarcadores , Progressão da Doença

RESUMO

OBJECTIVE: Liver cancer is the fifth most common cancer in the world. Research on the pathogenesis and detailed molecular mechanisms of liver cancer is very important. The immune system plays an important role in regulating the incidence and metastasis of liver cancer. MATERIALS AND METHODS: This work collected 20 blood samples from patients with clinical hepatocellular carcinoma without metastasis, 20 blood samples from patients with metastatic hepatocellular carcinoma, and 20 blood samples from healthy subjects. Flow cytometry was used to analyze the content of Treg and Th2 cells in the three groups of blood samples. Immunofluorescence was applied to analyze the relative expression of CTLA-4 and CD28 in lymphocytes of each group of blood samples. Western blot was used to analyze the T cell surface protein CTLA-4, CD28, GATA3, and FOXP3 expression in each group of blood samples. RESULTS: The expression of CD28 and GATA3 in the blood of patients with hepatocellular carcinoma without metastasis was obviously higher than that of patients with metastasis of hepatocellular carcinoma, which is contrary to the expression trend of CTLA-4 and FOXP3, and corresponds to the content ratio of Treg and Th2 cells, thus verifying the relationship between Treg/Th2 ratio and metastasis of hepatocellular carcinoma. CONCLUSIONS: In the microenvironment of liver cancer, the ratio of Treg/Th2 will increase significantly, thereby promoting the metastasis of hepatocellular carcinoma.

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OBJETIVO: El cáncer de hígado es el quinto cáncer más común en el mundo. La investigación sobre la patogenia y los mecanismos moleculares detallados del cáncer de hígado es muy importante. El sistema inmunológico juega un papel importante en la regulación de la incidencia y metástasis del cáncer de hígado. MATERIAL Y MÉTODOS: Este trabajo recogió 20 muestras de sangre de pacientes con carcinoma hepatocelular clínico sin metástasis, 20 muestras de sangre de pacientes con carcinoma hepatocelular metastásico y 20 muestras de sangre de sujetos sanos. Se utilizó citometría de flujo para analizar el contenido de células Treg y Th2 en los tres grupos de muestras de sangre. Se aplicó inmunofluorescencia para analizar la expresión relativa de CTLA-4 y CD28 en linfocitos de cada grupo de muestras de sangre. Se utilizó Western blot para analizar la expresión de la proteína de superficie de células T CTLA-4, CD28, GATA3, FOXP3 en cada grupo de muestras de sangre. RESULTADOS: La expresión de CD28 y GATA3 en la sangre de pacientes con carcinoma hepatocelular sin metástasis fue obviamente mayor que la de pacientes con metástasis de carcinoma hepatocelular, lo cual es contrario a la tendencia de expresión de CTLA-4 y FOXP3, y corresponde al contenido relación de células Treg y Th2, verificando así la relación entre la relación Treg/Th2 y la metástasis del carcinoma hepatocelular. CONCLUSIONES: En el microambiente del cáncer de hígado, la proporción de Treg/Th2 aumentará significativamente, promoviendo así la metástasis del carcinoma hepatocelular.

Assuntos

Carcinoma Hepatocelular , Neoplasias Hepáticas , Carcinoma Hepatocelular/patologia , Humanos , Neoplasias Hepáticas/patologia , Linfócitos T Reguladores/metabolismo , Linfócitos T Reguladores/patologia , Microambiente Tumoral

RESUMO

BACKGROUND: Methylisothiazolinone (MI) and Methylchloroisothiazolinone (MCI) are among the most common skin sensitizers, yet the immunological events that occur during MCI/MI allergic contact dermatitis (ACD) are still poorly understood. OBJECTIVES: To analyse dendrocytes, macrophage subtypes and T cells in skin during the elicitation phase of MCI/MI ACD. METHODS: Thirteen patients with positive patch test reactions to MCI/MI (ACD group) and 11 individuals with negative patch test results were selected. Skin biopsies were only performed at 48 hours of patch testing. Immunohistochemistry was conducted to assess T cells, dendrocytes (Factor XIIIa), M1 (p-Stat1, CD68) and M2 (c-Maf, CD163) macrophages. Transcriptional analyses were performed for cytokines and related factors, and further compared to atopic dermatitis samples (n=4). Immunofluorescence assays addressed T cells location, along with IL-4 or IL-13, within the skin. RESULTS: MCI/MI elicited dermal dendrocytes and macrophages, pronouncedly the M2 subtype. T cells, majorly CD4+ T cells, accumulated in the perivascular areas. Similarly, abundant IL-4 protein was detected in these areas. There was an upregulation of IL-4 and IL-13 mRNA expression, a mild increase in IFNG mRNA levels and a down-regulation of RORC in the ACD group. Immunofluorescence revealed dermal clusters of T cells co-localized with IL-4. CONCLUSIONS: M2 macrophages and Th2 cells participate in the immunopathogenesis of MCI/MI ACD. Dermal dendrocytes and M2 macrophages may assist the formation of CD4+ T cells perivascular clusters. These findings render a mechanistic insight into the MCI/MI reaction. Further analysis at different timepoints of patch testing is required to fully comprehend this ACD kinetics.

Assuntos

Dermatite Alérgica de Contato , Interleucina-4 , Humanos , Interleucina-13 , Macrófagos , Testes do Emplastro/efeitos adversos , Testes do Emplastro/métodos , RNA Mensageiro , Células Th2 , Tiazóis

RESUMO

A rinossinusite crônica (RSC) é uma síndrome caracterizada pela inflamação da mucosa nasal e dos seios paranasais por pelo menos 12 semanas, acometendo de 5% a 12% da população geral. A síndrome é associada a alta morbidade e considerada um grande problema de saúde pública devido a sua prevalência, seu custo para a sociedade e ao impacto que acarreta na qualidade de vida dos pacientes e em seu desempenho escolar ou profissional. Ademais, a RSC está associada a diversas comorbidades, como dermatite atópica, distúrbios respiratórios do sono, conjuntivite, otite média, asma e problemas emocionais. O dupilumabe é eficaz e seguro no tratamento da RSC com polipose nasal. A eficácia é progressiva no primeiro ano de tratamento, e a posologia de 300 mg a cada duas semanas é superior em relação à de cada quatro semanas. A interrupção do tratamento com 24 semanas acarreta a perda parcial de seus efeitos benéficos. O imunobiológico também é eficaz no controle da asma nos pacientes que apresentam essa doença como comorbidade. Alguns pacientes podem apesentar aumento transitório de eosinófilos sanguíneos, e 2,7% desenvolveram conjuntivite como reação adversa nos estudos SINUS-24 e SINUS-52. O dupilumabe é uma excelente opção terapêutica no tratamento concomitante de múltiplas doenças caracterizadas pela inflamação de tipo II.

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Chronic rhinosinusitis (CRS) is a syndrome characterized by inflammation of the nasal mucosa and paranasal sinuses for at least 12 weeks, affecting 5% to 12% of the general population. The syndrome is associated with high morbidity and is considered a major public health problem because of its prevalence, its cost to society, and the impact it has on patients' quality of life and on their school or professional performance. Furthermore, CRS is associated with several comorbidities, such as atopic dermatitis, sleep-disordered breathing, conjunctivitis, otitis media, asthma, and emotional problems. Dupilumab is effective and safe in the treatment of CRS with nasal polyposis. Effectiveness is progressive in the first year of treatment, and a dosage of 300 mg every two weeks is more effective than that of every four weeks. Discontinuing treatment at 24 weeks results in partial loss of its beneficial effects. The biological drug is also effective in controlling asthma in patients who have this disease as a comorbidity. Some patients may experience a transient increase in blood eosinophils, and 2.7% developed conjunctivitis as an adverse reaction in the SINUS-24 and SINUS-52 studies. Dupilumab is an excellent therapeutic option in the concomitant treatment of multiple diseases characterized by type II inflammation.

Assuntos

Humanos , Rinite , Pólipos Nasais , Anticorpos Monoclonais Humanizados , Otite Média , Seios Paranasais , Pacientes , Qualidade de Vida , Asma , Sinusite , Terapêutica , Efetividade , Conjuntivite , Dermatite Atópica , Eosinófilos , Mucosa Nasal

RESUMO

INTRODUCTION: Major depressive disorder (MDD) can impact the severity of allergic rhinitis (AR) and asthma (AA). Here, we evaluated the cytokine production by T-cells from AR and AA patients with or without MDD. The effect of serotonin on the in vitro T-cell response was also evaluated. METHODS: The cytokines produced by activated T-cells were measured by Luminex and flow cytometry. In some cell cultures, serotonin was added. RESULTS: MDD not only enhanced the production of Th2- and Th17-related cytokines, but also, the levels of interleukin (IL)-5 and IL-17 were directly correlated with the severity of depression and anxiety symptoms. As compared with AR, the levels of IL-17 were higher and the release of IL-10 was lower in activated T-cell cultures from AA patients, mainly those with MDD. In AA/MDD patients, the severity of anxiety symptoms and lung disease was directly correlated with Th17-like and hybrid Th2/Th17 cells, but inversely correlated with IL-10-secreting CD4+ T-cells. Finally, the addition of serotonin reduced the production of Th2- and Th17-related cytokines, but elevated IL-10 secretion in cell cultures from both AR and AA patients. CONCLUSIONS: Our findings suggest that not only the occurrence of MDD but also the severity of anxiety symptoms, may adversely affect the outcome of allergic reactions by favoring the production of cytokines implicated in the pathogenesis of AR and AA, a phenomenon that was attenuated by serotonin.

Assuntos

Asma/psicologia , Citocinas/metabolismo , Transtorno Depressivo Maior/imunologia , Rinite Alérgica/psicologia , Células Th17/imunologia , Células Th2/imunologia , Adulto , Ansiedade/complicações , Ansiedade/imunologia , Ansiedade/psicologia , Asma/complicações , Asma/diagnóstico , Asma/imunologia , Biomarcadores/metabolismo , Estudos de Casos e Controles , Transtorno Depressivo Maior/complicações , Transtorno Depressivo Maior/diagnóstico , Transtorno Depressivo Maior/psicologia , Feminino , Citometria de Fluxo , Humanos , Masculino , Pessoa de Meia-Idade , Gravidade do Paciente , Rinite Alérgica/complicações , Rinite Alérgica/diagnóstico , Rinite Alérgica/imunologia , Serotonina/farmacologia , Agonistas do Receptor de Serotonina/farmacologia , Células Th17/efeitos dos fármacos , Células Th2/efeitos dos fármacos

RESUMO

Individuals carrying the ATC/TTC haplotype (Hap-1) in the interleukin 8 (IL8) gene were reported as more susceptible to chronic periodontitis (CP), an infectious disease associated with Gram-negative bacteria, in comparison to patients with the ATT/TTC haplotype (Hap-2). This study investigated the functionality of the IL8 haplotypes in lymphocytes and monocytes of individuals carrying the Hap-1 or Hap-2 IL8 haplotypes in the response to CP-associated Gram-negative bacteria (periodontopathogens). Peripheral blood was collected from 6 subjects carrying each haplotype, and their immune cells were challenged with periodontopathogens or phorbol 12-myristate 13-acetate (PMA) plus Ionomycin. Depending on the immune cell type (lymphocytes or monocyte-derived macrophages) the assessed outcomes were: phenotypical polarization, gene expression, phagocytic activity, chemotaxis and production of reactive oxygen species (ROS). Subjects carrying the Hap-1 haplotype showed increased expression of IL8 and TNFA and significantly skewing towards pro-inflammatory Th1/M1/Th17 phenotypes. There was increased percentage of ROS-producing monocyte-derived macrophages from individuals carrying the Hap-1 haplotype. Cells from individuals presenting the Hap-2 haplotype had an overall attenuated response to periodontopathogens, with a significant shift towards the Treg phenotype. In conclusion, the IL8 haplotypes showed to be functional both in monocyte-derived macrophages and lymphocytes. The Hap-1 haplotype previously associated with increased susceptibility to CP demonstrated greater skewing to pro-inflammatory Th1/M1/Th17 phenotypes and production of ROS.

Assuntos

Periodontite Crônica , Bactérias Gram-Negativas/imunologia , Bactérias Gram-Negativas/patogenicidade , Interleucina-8/genética , Linfócitos/metabolismo , Macrófagos/metabolismo , Aggregatibacter actinomycetemcomitans/imunologia , Aggregatibacter actinomycetemcomitans/patogenicidade , Periodontite Crônica/genética , Periodontite Crônica/imunologia , Periodontite Crônica/microbiologia , Feminino , Predisposição Genética para Doença , Infecções por Bactérias Gram-Negativas/genética , Infecções por Bactérias Gram-Negativas/imunologia , Haplótipos , Humanos , Interleucina-8/metabolismo , Linfócitos/imunologia , Macrófagos/imunologia , Masculino , Pessoa de Meia-Idade , Monócitos/imunologia , Monócitos/metabolismo , Fenótipo , Porphyromonas gingivalis/imunologia , Porphyromonas gingivalis/patogenicidade

RESUMO

BACKGROUND: The mechanisms of activation and regulation of T lymphocytes and their cytokines in malaria caused by Plasmodium vivax are complex and poorly understood. Previous data suggest that T cells balance protective immune responses with immune mediated pathology in malaria. This study investigates the lymphocytic profile of patients infected with P. vivax by identifying and quantifying the specific sub-populations of Th1, Th2, Th17 and Treg cells and observing the correlation between parasitaemia and the number of platelets. METHODS: A cross-sectional study was carried out in an endemic area of the state of Acre, Brazil. In order to obtain identification and quantification of lymphocyte sub-populations through flow cytometry, blood samples were collected from 50 individuals infected with P. vivax and 20 non-infected controls. To differentiate Th1 from Th2, the presence of cytokines IL-4 and TNF was examined by enzyme-linked immunosorbent assay. Utilizing the Mann-Whitney and Spearman coefficient tests, comparison and correlation analysis were rendered to test the parasitaemia and the number of platelets relationship. RESULTS: The data indicate that individuals infected with P. vivax present a significant reduction in Th1, Th2 and Th17 cell sub-populations when compared to the non-infected control group. A negative correlation exists between parasitaemia and platelet counts in individuals infected with P. vivax. There is no correlation of parasitaemia or thrombocytopaenia with any sub-population of T lymphocytes analysed. Interestingly, patients with serum Th1 cytokine profile present inversely proportional parasitaemia to the increase in the number of Th1, Th2, Th17 and Treg cells while patients with serum Th2 cytokine profile present directly proportional parasitaemia to the increase in number of Th1 and Th2 cells. Regarding the number of platelets, patients with serum Th1 cytokine profile show a correlation directly proportional to the Th17 sub-population. In contrast, platelet counts are directly proportional only to Treg and activated Treg cells in patients with serum Th2 cytokine profile. CONCLUSIONS: During the P. vivax infection patients with serum Th1 versus Th2 cytokine profile present different biological mechanisms for activating the immune system against parasite load.

Assuntos

Subpopulações de Linfócitos/imunologia , Malária Vivax/imunologia , Malária Vivax/patologia , Parasitemia/imunologia , Parasitemia/patologia , Plasmodium vivax/imunologia , Trombocitopenia/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Brasil , Estudos Transversais , Ensaio de Imunoadsorção Enzimática , Feminino , Citometria de Fluxo , Humanos , Interleucina-4/sangue , Masculino , Pessoa de Meia-Idade , Fator de Necrose Tumoral alfa/sangue , Adulto Jovem

RESUMO

In a state of oxidative stress, there is an increase of reactive species, which induce an altered intracellular signaling, leading to dysregulation of the inflammatory response. The inability of the antioxidant defense systems to modulate the proinflammatory response is key to the onset and progression of neurodegenerative diseases. The aim of this work is to review the effect of the state of oxidative stress on the loss of regulation of the inflammatory response on the microglia and astrocytes, the induction of different CD4+T cell populations in neuroinflammation, as well as its role in some neurodegenerative diseases. For this purpose, an intentional search of original articles, short communications, and reviews, was carried out in the following databases: PubMed, Scopus, and Google Scholar. The articles reviewed included the period from 1997 to 2017. With the evidence obtained, we conclude that the loss of redox balance induces alterations in the differentiation and number of CD4+T cell subpopulations, leading to an increase in Th1 and Th17 response. This contributes to the development of neuroinflammation as well as loss of the regulation of the inflammatory response in neurodegenerative diseases such as Alzheimer's (AD), Parkinson's (PD), and Multiple Sclerosis (MS). In contrast, regulatory T cells (Tregs) and Th2 modulate the inflammatory response of effect of T cells, microglia, and astrocytes. In this respect, it has been found that the mobilization of T cells with anti-inflammatory characteristics toward damaged regions of the CNS can provide neuroprotection and become a therapeutic strategy to control inflammatory processes in neurodegeneration.

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Abstract Introduction Eosinophilic and noneosinophilic Nasal polyps (NPs) are different subtypes of NPs and require different treatment methods. Objective To compare the histologic characteristics, mRNA and protein expression between Nasal Polyps with and without eosinophilia. Methods NPs tissues were obtained from eighty-six NPs patients during surgery. Eosinophilic and noneosinophilic NPs were distinguished according to immunochemical results of the specimen. The histological, mRNA and protein expression features were compared between the two groups. Results In eosinophilic NPs, we observed a significantly higher GATA-3, IL-5, IL-4, IL-13 mRNA and protein expression. In noneosinophilic NPs, IL-17, IL-23 and RORc mRNA and protein expression were increased. Immunohistochemistry tests showed, more mast cells and less neutrophils in eosinophilic NPs compared with noneosinophilic NPs. Eosinophilic NPs patient presented more severe symptom scores when compared to noneosinophilic NPs. Conclusion We demonstrate for the first time that Th2 is the predominant reaction in eosinophilic NPs while Th17 is the predominant reaction in noneosinophilic NPs. Our study may provide new treatment strategy for NPs.

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Resumo Introdução Pólipos nasais (PNs) eosinofílicos e não eosinofílicos são diferentes subtipos de PNs e requerem diferentes métodos de tratamento. Objetivo Comparar as características histológicas e a expressão de mRNAs e proteínas entre PNs com e sem eosinofilia. Método Amostras de PNs foram obtidos de 86 pacientes durante a cirurgia. PNs eosinofílicos e não eosinofílicos foram diferenciados segundo os resultados imunoistoquímicos de cada amostra. As características histológicas e de expressão de mRNAs e de proteínas foram comparadas entre os dois grupos. Resultados Em PNs eosinofílicos, observamos uma expressão significativamente maior dos mRNAs e proteínas GATA-3, IL-5, IL-4 e IL-13. Nos PNs não eosinofílicos, aumentou a expressão dos mRNAs e das proteínas IL-17, IL-23 e RORc. Nos testes imunoistoquímicos, observamos maior número de mastócitos e menor número de neutrófilos nos PNs eosinofílicos, em comparação com PNs não eosinofílicos. Os pacientes com PNs eosinofílicos obtiveram escores de sintomas mais graves vs. PNs não eosinofílicos. Conclusão Demonstramos, pela primeira vez, uma reação Th2 predominante em PNs eosinofílicos e uma reação Th17 predominante em PNs não eosinofílicos. Nosso estudo pode proporcionar novas estratégias terapêuticas para a rinossinusite crônica.

Assuntos

Humanos , Masculino , Feminino , Adulto , Sinusite/imunologia , Rinite/imunologia , Pólipos Nasais/imunologia , Eosinófilos/imunologia , Sinusite/complicações , Fatores de Transcrição , Índice de Gravidade de Doença , RNA Mensageiro/metabolismo , Imuno-Histoquímica , Rinite/complicações , Pólipos Nasais/complicações , Pólipos Nasais/metabolismo , Pólipos Nasais/patologia , Doença Crônica , Citocinas/imunologia , Linfócitos T Auxiliares-Indutores/imunologia , Eosinofilia/complicações , Eosinofilia/metabolismo , Eosinofilia/patologia , Reação em Cadeia da Polimerase em Tempo Real

RESUMO

INTRODUCTION: Eosinophilic and noneosinophilic Nasal polyps (NPs) are different subtypes of NPs and require different treatment methods. OBJECTIVE: To compare the histologic characteristics, mRNA and protein expression between Nasal Polyps with and without eosinophilia. METHODS: NPs tissues were obtained from eighty-six NPs patients during surgery. Eosinophilic and noneosinophilic NPs were distinguished according to immunochemical results of the specimen. The histological, mRNA and protein expression features were compared between the two groups. RESULTS: In eosinophilic NPs, we observed a significantly higher GATA-3, IL-5, IL-4, IL-13 mRNA and protein expression. In noneosinophilic NPs, IL-17, IL-23 and RORc mRNA and protein expression were increased. Immunohistochemistry tests showed, more mast cells and less neutrophils in eosinophilic NPs compared with noneosinophilic NPs. Eosinophilic NPs patient presented more severe symptom scores when compared to noneosinophilic NPs. CONCLUSION: We demonstrate for the first time that Th2 is the predominant reaction in eosinophilic NPs while Th17 is the predominant reaction in noneosinophilic NPs. Our study may provide new treatment strategy for NPs.

Assuntos

Eosinofilia/imunologia , Pólipos Nasais/imunologia , Rinite/imunologia , Sinusite/imunologia , Adulto , Doença Crônica , Citocinas/imunologia , Eosinofilia/complicações , Eosinofilia/metabolismo , Eosinofilia/patologia , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pólipos Nasais/complicações , Pólipos Nasais/metabolismo , Pólipos Nasais/patologia , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Rinite/complicações , Índice de Gravidade de Doença , Sinusite/complicações , Linfócitos T Auxiliares-Indutores/imunologia , Fatores de Transcrição

RESUMO

O diabetes mellitus tipo 1 (DM1) é uma doença autoimune crônica, onde as células T autorreativas destroem as células beta pancreáticas levando à dependência de insulina exógena. Para o desenvolvimento do DM1 são necessárias numerosas interações entre as células do sistema imunológico, principalmente mediadas por citocinas de resposta T helper 1 (Th1) e T helper 2 (Th2). O presente estudo teve como objetivo analisar a relação das citocinas de resposta Th1 e Th2 no desenvolvimento do DM1 por meio de uma revisão de literatura, avaliando artigos científicos eletrônicos publicados entre os anos de 2001 e 2016, além de livros de imunologia aplicados à clínica. Diversos estudos na literatura demonstram que o perfil de secreção de citocinas durante o desenvolvimento do DM1 é de padrão Th1 onde temos como principais constituintes a IL-2 e o IFN-y. Já as citocinas de resposta Th2, compostas basicamente pela IL-4, IL-6 e IL-10, são responsáveis por bloquear a evolução do DM1. Através desses dados conclui-se que o entendimento dos aspectos imunológicos constitui a base para detecção e prevenção do DM1, sendo a disponibilidade de citocinas clonadas e purificadas uma nova perspectiva para terapias clínicas específicas para modular a resposta imune

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Type 1 diabetes mellitus (DM1) is a chronic autoimmune disease, where as autoreactive T cells destroy as pancreatic beta cells leading to exogenous insulin dependence. For the development of DM1, interactions between immune system cells, mainly mediated by cytokines of T helper 1 (Th1) and T helper 2 (Th2) are required. The present study aimed to analyze the relationship of Th1 and Th2 response cytokines in the development of DM1, through a review of the literature, evaluating electronic scientific articles published between 2001 and 2016, as well as immunology books applied to the clinic. Several studies in the literature demonstrate that the cytokine secretion profile during the development of DM1 is of the Th1 pattern where we have as main constituent of IL-2 and IFN-γ. As Th2 response cytokines, composed mainly of IL-4, IL-6 and IL-10, they are responsible for blocking the progression of DM1. Through conclusive data, it is a point of view for the prevention of DM1. With the availability of cloned and purified cytokines a new perspective for specific clinical therapies to modulate the immune response

Assuntos

Citocinas , Células Th2 , Células Th1 , Diabetes Mellitus Tipo 1

RESUMO

Un tercio de la población mundial poseen anticuerpos contra Toxoplasma gondii. El hombre se infecta a través de los esporozoitos provenientes de las heces de los gatos que contaminan la tierra, frutas, verduras y al agua; de los bradizoitos presentes en carnes que lo infectan cuando la consume poco cocinada o por su manipulación y por trofozoitos circulantes durante la fase hematógena en el hombre, infecta al feto a través de la placenta y a individuos seronegativos por órganos sólidos trasplantados o transfundidos con elementos formes de la sangre; son los llamados grupos de riesgos los más vulnerables a desarrollar formas graves de esta enfermedad que los puede conducir a la muerte. Estudios resientes corroboran la relación de esta infección con trastornos neurosiquiatricos, en particular con la esquizofrenia, así como su relación con accidentes de tránsito en conductores seropositivos; es de gran importancia tener presente las formas de adquirir la enfermedad y las medidas de precaución sobre todo cuando se ha demostrado que nunca se ha padecido la enfermedad.

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One third of the world population have antibodies against Toxoplasma gondii. Human beings may be infected by sporozoites from cat faeces contaminating the ground, fruits, vegetables and water, by bradyzoites present in insufficiently cooked or improperly manipulated meat, or by trophozoites circulating during the hematogenous phase. Fetuses may be infected through the placenta, and seronegative individuals by solid organs transplanted or transfused with formed elements of the blood. These are the risk groups most prone to develop serious, life-threatening forms of the disease. Recent studies confirm the relationship of this infection to neuropsychiatric disorders, particularly schizophrenia, as well as its relationship to traffic accidents among seropositive drivers. It is paramount to bear in mind the ways in which the disease may be acquired and the corresponding prevention measures, especially for persons who have never had the disease.

RESUMO

Aim: To evaluate the involvement of Th2 cells in different periods of the active phase of experimental periodontal disease and expression of the R1 subunit of the receptor for IFN-γ during the early and advanced progression of the disease. Methods: Experimental periodontitis was induced in 30 male Wistar rats by placing cotton ligatures around the mandibular first molars. The rats were then randomly assigned into two groups: G1=15 and G2=15, in group G1, ligatures were maintained for 2 days, a period that corresponds to the initial stage of periodontal disease in rats, in G2 ligatures were left for 15 days, a period that corresponds to the advanced stage of periodontal disease. The contra-lateral teeth served as controls (unligated). An immunohistochemical investigation of the gingival tissue was performed to detect the presence of the Th2 specific transcription factor (GATA3). Results Light microscopy analysis revealed a decreased expression of GATA-3-positive cells when bone loss progressed. IFN-γ R1 was detected at an early stage during the active phase of disease, but the expression of positive cells remained unaltered during the remaining period of the study.

Assuntos

Animais , Ratos , Citocinas , Imuno-Histoquímica , Doenças Periodontais , Periodontite/patologia , Células Th1

RESUMO

The NFAT family of transcription factors plays a central role in the regulation of cytokine gene expression during the immune response. NFAT functions have been extensively explored in lymphocyte activation and differentiation, but the involvement of NFAT proteins in dendritic cells (DCs) is still not well known. Here, we investigated the role of the NFAT1 transcription factor in murine DCs. Initially, we demonstrated by western blot that the NFAT1 protein is present in splenic DCs and is rapidly activated upon calcium influx. We then used NFAT1-deficient mice (NFAT1-/-) to investigate whether NFAT1 influences the ability of DCs to induce Th differentiation. Our data demonstrated that NFAT1-/- DCs showed an increased capacity to differentiate CD4 T cells to the Th1 phenotype. CD4 cells that were primed in vitro with NFAT1-/- DCs had increased IFN-γ production. The same results were observed when the CD4 cells were primed in vivo through the sensitization of NFAT1-/- mice with ovalbumin. Furthermore, our results demonstrated that the cytokine IL-12 is one of the factors involved in this process because its production is increased in NFAT1-/- mice, and neutralizing anti-IL-12 antibodies almost completely eliminated the IFN-γ production. These results demonstrated that the NFAT1 transcription factor regulates specific functions in DCs that are involved in CD4 differentiation, suggesting that the inhibition of NFAT1 in DCs may be used as a therapy to modulate specific immune responses.

Assuntos

Diferenciação Celular/imunologia , Células Dendríticas/imunologia , Fatores de Transcrição NFATC/imunologia , Linfócitos T Auxiliares-Indutores/imunologia , Animais , Western Blotting , Células Cultivadas , Células Dendríticas/metabolismo , Imunofluorescência , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Fatores de Transcrição NFATC/metabolismo , Linfócitos T Auxiliares-Indutores/citologia

RESUMO

Any therapeutic vaccination approach against HIV-1 must induce CTL and Th1 cells. But, therapeutic vaccination is more than that. For extensive application of a therapeutic vaccine several questions need to be solved in advance to achieve a global impact. In this commentary some of them are addressed. We analyze the epidemiology, sociology, economy and immunopathology related to the HIV/AIDS disease. Also, important technical issues and real possibilities to overcome at least some of the major limitation of the antiretroviral treatments in the pursuit of an effective vaccine are considered. From the integration of previous analyses some conclusions are drawn. Because it is just a commentary some arguments are not unveiled into their full extension. At the end, we discuss some issues in relation to the development of the vaccine candidate TERAVAC-HIV-1 as a case study.

Assuntos

Vacinas contra a AIDS/uso terapêutico , Síndrome da Imunodeficiência Adquirida/prevenção & controle , Anticorpos Anti-HIV/imunologia , Células Th1/imunologia , Síndrome da Imunodeficiência Adquirida/epidemiologia , Síndrome da Imunodeficiência Adquirida/imunologia , Fármacos Anti-HIV/uso terapêutico , Terapia Antirretroviral de Alta Atividade , Infecções por HIV/imunologia , Infecções por HIV/prevenção & controle , HIV-1/imunologia , Humanos , Vacinação

RESUMO

Os mastócitos são tipos celulares que executam uma série de funções por meio da liberação de mediadores químicos, quando devidamente estimulados, interagindo com várias células das mais diferentes origens. Sabe-se, ainda, que as interações entre mastócitos e células T existem, porém ainda não são muito claras. O objetivo deste trabalho foi o de realizar uma revisão de literatura dos aspectos atuais a respeito da possível relação entre mastócitos e células T em processos inflamatórios.

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The mast cells are cellular types that execute a series of functions through the release of chemical mediators when duly stimulated, interacting with some cells of the most different origins. It is known despite the interactions between mast cells and cells T exist, however aren't very clear yet. The objective of this work was to carry through a literary revision of the related current aspects of a possible relationship between mast cells and T cells in inflammatory process.

Assuntos

Células Th1 , Linfócitos T , Mastócitos

RESUMO

Diversos estudios en modelos de ratones han demostrado que la inmunidad protectora frente a Leishmania es mediada por linfocitos T, células presentadoras de antígeno y citocinas. Sin embargo, pocos estudios se han realizado para evaluar citocinas en perros infectados en forma natural con Leishmania infantum/chagasi. El perro doméstico es el principal reservorio del parásito, en tal sentido, el objetivo de este trabajo fue determinar las citocinas en suero de 33 perros con Leishmaniasis Visceral Canina (LVC), provenientes del estado Nueva Esparta, Venezuela (foco endémico). Los perros fueron clasificados en sintomáticos o asintomáticos, de acuerdo al análisis de los signos clínicos de la enfermedad, coincidentes con los títulos de anticuerpos contra las kinesinas recombinantes de Leishmania rK39 y rK26. Otros dos grupos incluyeron: 10 perros de la misma zona endémica como grupo control endémico (CE) y 10 perros de la zona no endémica como control sano (CS). Las concentraciones (pg/mL) de las citocinas solubles IFN-γ, TNF-α, IL-10, IL-6, IL-4 e IL-2 se determinaron por citometría de flujo (Kit CBA Hu Th1/Th2, BD TM). Los resultados mostraron concentraciones estadísticamente mayores (p<0,05) de IFN-γ (69,93±7,46), IL-4 (7,51±2,68), TNF-α (3,86±1,46) e IL-2 (39,85±3,84) en el grupo de perros asintomáticos, con respecto a los perros sintomáticos (60,8±10,6; 5,28±0,80; 2,76±0,72 y 36,04±3,61, respectivamente) y los perros sanos (51±14; 4,65±0,2; 3,21±0,89 y 32,65±5,86, respectivamente). Los perros asintomáticos también presentaron mayor concentración de IL-6 (4,9±0,55) que los CS (4,02±0,64) (p<0,01). Estos resultados demuestran que los perros en estado asintomático exhiben mayor proporción de citocinas de activación celular y proinflamatorias. Los resultados señalan a la medición de citocinas séricas como reflejo del estado inmunológico de los caninos en futuros estudios orientados a vacunación o terapia.

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Different experimental murine models have shown that protective immunity against Lesihmania depends upon T cells, cytokines, and antigen presenting cells. However, the role of cytokines in naturally-infected hosts like domestic dogs is controversial. Few studies have evaluated cytokines in dogs naturally-infected with Leishmania infantum/chagasi. Since the domestic dog is the main reservoir of the parasite, a study was conducted to determine cytokines in serum of 33 dogs with Canine Visceral Lesihmaniasis from endemic areas of the State of Nueva Esparta, Venezuela. Dogs were classified as symptomatic (SD) and asymptomatic (AD), according to the expression of three or more clinical signs and levels of  antibodies for rK39 and rK26. Ten non-infected, rK39 negative controls were included from an endemic area (EA) and ten dogs from a non-endemic area were used as healthy controls (HC). The following cytokines (pg/mL) were measured in serum by flow cytometry (CBA Hu Th1/Th 2, BD TM kit): IFN-γ, TNF-α, IL-10, IL-6, IL-4 and IL-2. Results show a higher  concentration (P<0.05) of  IFN-γ (69.93±7.46), IL-4 (7.51±2.68), TNF-α (3.86±1.46), and IL-2 (39.85±3.84) in AD when compared with SD (60.8±10.6; 5.28±0.80; 2.76± 0.72; and 36.04±3.61, respectively); and HC (51±14; 4.65±0.2; 3.21±0.89, and 32.65±5.86, respectively). The AD also showed higher levels (P<0.01) of IL-6 (4.9±0.55) compared with HC (4.02±0.64). Results show that AD exhibit a higher proportion of cellular activation and proinflammatory cytokines. Results indicate that measuring of serum cytokines could reflect the immunological status in dogs in future clinical trials oriented to either vaccination or therapy.