RESUMO
Real-world data on anatomically localized psoriasis and its response to systemic therapy across different age-groups and sexes is limited. This study aimed to evaluate the severity and distribution of psoriasis over time in female and male patients receiving systemic therapies, categorized by age within the Swiss psoriasis registry (SDNTT). Patient-data was obtained over 11 years through the SDNTT. The localized Psoriasis Area and Severity Index (locPASI) of the head, trunk, upper and lower extremities was analyzed over two years following the start of systemic non-/biologic treatment. A total of 316 female and 517 male patients were analyzed. Male patients had a higher baseline locPASI for legs, trunk and arms (p < 0.001), but not for the head (p = 0.961). The locPASI for the head in younger female patients (18-40 years) had a higher score than those aged 55 + (p = 0.022) and after two years, middle aged (41-54) showed a lower score compared to younger patients (p = 0.045). Younger male patients revealed a lower score after two years of therapy in the leg- and arm-area compared to older (p = 0.018 and p = 0.048, respectively). Female patients on non-biologics had a fast initial response, converging with male patients' scores over 24 months. Over 75% locPASI reduction was observed for female head-area (81.4%), male trunk (82.7%) and legs (76.1%). Absolute locPASI ≤ 2 was achieved 3-6 months for all locations with interleukin (IL)-17, IL-12/23 and IL-23-inhibitors, except for the legs of male patients on anti-IL-17 and female patients on anti-IL-12/23 and -IL-23. After two years, male patients did not achieve a locPASI ≤ 2 for any biologic-treatment in the legs, nor for the arms on anti-TNF-α. Significant disparities in localized PASI were observed between female and male patients. The age, sex and severity of distinct localizations should be considered to optimize treatment goals.
Assuntos
Psoríase , Sistema de Registros , Índice de Gravidade de Doença , Humanos , Psoríase/tratamento farmacológico , Psoríase/diagnóstico , Psoríase/imunologia , Psoríase/epidemiologia , Masculino , Feminino , Sistema de Registros/estatística & dados numéricos , Adulto , Pessoa de Meia-Idade , Suíça/epidemiologia , Adulto Jovem , Fatores Sexuais , Adolescente , Fatores Etários , Idoso , Fármacos Dermatológicos/uso terapêuticoRESUMO
As potent pro-inflammatory mediators, IL-17 family cytokines play crucial roles in the pathogenesis of various inflammatory and autoimmune skin disorders. Although substantial progress has been achieved in understanding the pivotal role of IL-17A signaling in psoriasis, leading to the development of highly effective biologics, the functions of other IL-17 family members in inflammatory or autoimmune skin diseases remain less explored. In this review, we provide a comprehensive overview of IL-17 family cytokines and their receptors, with a particular focus on the recent advancements in identifying cellular sources, receptors and signaling pathways regulated by these cytokines. At the end, we discuss how the aberrant functions of IL-17 family cytokines contribute to the pathogenesis of diverse inflammatory or autoimmune skin diseases.
Assuntos
Doenças Autoimunes , Interleucina-17 , Transdução de Sinais , Dermatopatias , Humanos , Interleucina-17/metabolismo , Interleucina-17/imunologia , Doenças Autoimunes/imunologia , Doenças Autoimunes/metabolismo , Animais , Dermatopatias/imunologia , Dermatopatias/metabolismo , Psoríase/imunologia , Psoríase/metabolismo , Inflamação/imunologia , Inflamação/metabolismo , Receptores de Interleucina-17/metabolismo , Receptores de Interleucina-17/imunologiaRESUMO
To investigate the causality between B cell count and psoriasis by Mendelian randomization (MR). Collected B cell count and psoriasis data from IEU Open GWAS Project. Employed inverse variance weighting (IVW), MR-Egger, WM, weighted mode for analysis, ensuring result robustness. Assessed horizontal pleiotropy with MR-Egger, detected outliers using MR-PRESSO and examined instrumental variables heterogeneity with Cochran's Q-test. The IVW method suggested an association between a genetically predicted memory B cell count and the risk of psoriasis vulgaris. IVW results also showed no causality between other exposure factors and the corresponding outcomes. Also, the global test of MR-PRESSO analysis showed a significant association between a genetically predicted transitional absolute B cell count and the lower risk of psoriasis vulgaris. MR-Egger regression showed that horizontal pleiotropy did not influence the analysis results. We found that memory B cell absolute counts are associated with a lower risk of psoriasis. These data further elucidate the role of memory B cells in psoriasis and provide new options for psoriasis treatment.
Assuntos
Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Psoríase , Psoríase/genética , Psoríase/imunologia , Humanos , Linfócitos B/imunologia , Linfócitos B/metabolismo , Polimorfismo de Nucleotídeo Único , Predisposição Genética para Doença , Contagem de Linfócitos , Fatores de RiscoRESUMO
The primary pathological features of psoriasis include excessive epidermal keratinocytes and infiltration of inflammatory cells, which are pivotal targets for psoriasis therapy. Astragaloside IV (AS-IV), the principal active compound of astragalus, exhibits anti-inflammatory, antioxidant, and immune-modulatory properties. This study aims to investigate AS-IV's anti--psoriatic effects and underlying mechanisms. Normal human epidermal keratinocytes (NHEKs) were stimulated with a combination of TNF-α, IL-17A, IL-1α, IL-22, and oncostatin M (M5) to replicate psoriatic keratinocyte pathology in vitro. Cell proliferation was assessed using CCK8 and EDU staining. Pro-inflammatory cytokine levels were measured via qRT-PCR. In addition, an imiquimod (IMQ)-induced psoriasis mouse model was utilized. Skin histology changes were evaluated with HE staining, while IL-6 and TNF-α levels in mouse serum were quantified using ELISA. NF-κB pathway protein expression was analyzed by western blotting. The results demonstrated that AS-IV inhibited M5-induced proliferation of NHEKs. AS-IV reduced M5-stimulated IL-1ß, IL-6, IL-8, TNF-α, IL-23, and MCP-1 expression in NHEKs. Moreover, M5-induced phosphorylation of IκBα and p65 was significantly attenuated by AS-IV. Furthermore, AS-IV application ameliorated erythema, scale formation, and epidermal thickening in IMQ-induced psoriasis-like mouse models. AS-IV also decreased IL-6 and TNF-α levels in mouse serum and inhibited IκBα and p65 phosphorylation in skin tissues. However, prostratin treatment reversed these effects. These findings underscore AS-IV's capacity to mitigate M5-induced NHEK proliferation and inflammation. AS-IV shows promise in alleviating IMQ-induced psoriasis-like skin lesions and inflammation by suppressing the NF-κB pathway.
Assuntos
Proliferação de Células , Citocinas , Modelos Animais de Doenças , Imiquimode , Queratinócitos , Psoríase , Saponinas , Triterpenos , Animais , Psoríase/tratamento farmacológico , Psoríase/induzido quimicamente , Psoríase/imunologia , Psoríase/patologia , Saponinas/farmacologia , Queratinócitos/efeitos dos fármacos , Queratinócitos/imunologia , Triterpenos/farmacologia , Humanos , Camundongos , Proliferação de Células/efeitos dos fármacos , Citocinas/metabolismo , NF-kappa B/metabolismo , Anti-Inflamatórios/farmacologia , Células Cultivadas , Transdução de Sinais/efeitos dos fármacos , Camundongos Endogâmicos BALB C , Pele/patologia , Pele/efeitos dos fármacos , Pele/imunologiaRESUMO
Psoriasis is a common chronic inflammatory skin disorder that primarily affects the skin, nails, and joints. Beyond its cutaneous manifestations, psoriasis is associated with several systemic comorbidities. Various factors can trigger or exacerbate psoriasis, including stress, infections, medications, and vaccinations. This article reports what is, to the best of the author's knowledge, the first known case of acute exacerbation of plaque-type psoriasis, presenting as guttate psoriasis (GP), following herpes zoster vaccination. A 52-year-old male with a history of longstanding plaque-type psoriasis developed a sudden flare of GP lesions 2 weeks after receiving the recombinant herpes zoster vaccine. Physicians should be vigilant for potential triggers of psoriasis exacerbation, with the recombinant herpes zoster vaccine being among them.
Assuntos
Vacina contra Herpes Zoster , Psoríase , Humanos , Masculino , Pessoa de Meia-Idade , Herpes Zoster/prevenção & controle , Vacina contra Herpes Zoster/efeitos adversos , Vacina contra Herpes Zoster/imunologia , Psoríase/diagnóstico , Psoríase/imunologia , Vacinas Sintéticas/efeitos adversos , Vacinas Sintéticas/imunologiaRESUMO
Many skin diseases begin with inflammatory changes on a molecular level. To develop a more thorough understanding of skin pathology and to identify new targets for therapeutic advancements, molecular mechanisms of inflammation in the context of skin disease should be studied. Current research efforts to better understand skin disease have focused on examining the role of molecular processes at several stages of the inflammatory response such as the dysregulation of innate immunity sensors, disruption of both transcriptional and post-transcriptional regulation, and crosstalk between immune and neuronal processes (neuro-immune crosstalk). This review seeks to summarize recent developments in our understanding of inflammatory processes in skin disease and to highlight opportunities for therapeutic advancements. With a focus on publications within the past 5 years (2019-2024), the databases PubMed and EBSCOhost were used to search for peer-reviewed papers regarding inflammatory molecular mechanisms and skin disease. Several themes of research interest regarding inflammatory processes in skin disease were determined through extensive review and were included based on their relative representation in current research and their focus on therapeutic potential. Several skin diseases such as psoriasis, atopic dermatitis, hidradenitis suppurativa, and scleroderma were described in the paper to demonstrate the widespread influence of inflammation in skin disease.
Assuntos
Inflamação , Dermatopatias , Humanos , Inflamação/patologia , Dermatopatias/patologia , Dermatopatias/imunologia , Dermatopatias/etiologia , Dermatopatias/metabolismo , Animais , Imunidade Inata , Pele/patologia , Pele/metabolismo , Pele/imunologia , Dermatite Atópica/patologia , Dermatite Atópica/imunologia , Dermatite Atópica/metabolismo , Dermatite Atópica/genética , Dermatite Atópica/etiologia , Psoríase/patologia , Psoríase/genética , Psoríase/metabolismo , Psoríase/imunologia , Psoríase/etiologiaRESUMO
Psoriasis is a chronic inflammatory skin condition associated with systemic inflammation and a higher risk of cardiovascular comorbidities. This study retrospectively evaluates coagulation parameters in psoriasis vulgaris patients treated with IL-17 inhibitors (secukinumab, ixekizumab) and IL-23 inhibitors (risankizumab, guselkumab), compared to those untreated systemically. The study reviewed records from 177 patients treated between January 2019 and March 2023. Patients were grouped into control (n = 77), secukinumab (n = 36), ixekizumab (n = 19), guselkumab (n = 24), and risankizumab (n = 21). Coagulation parameters, including PT, aPTT, PLT, MPV, INR, fibrinogen, D-dimer, and B12 levels, were analyzed. The primary endpoint was the comparison of coagulation parameters between groups. Significant differences were found in PT, with secukinumab-treated patients showing a significantly shorter PT compared to controls (p = 0.002). No significant differences were observed in other coagulation parameters across the groups. The study highlights a potential effect of secukinumab on coagulation pathways, possibly related to IL-17's role in inflammation and endothelial function. Despite current literature suggest a risk of cerebrovascular events with risankizumab, this study did not show any significant changes in coagulation parameters with risankizumab, indicating no hypercoagulability risk associated with this IL-23 inhibitor. Our findings suggest IL-17 and IL-23 inhibitors are generally safe concerning coagulation parameters, but regular monitoring may be warranted for patients on secukinumab due to its effect on PT. Further long-term studies are needed to fully understand the cardiovascular risks associated with these therapies.
Assuntos
Anticorpos Monoclonais Humanizados , Coagulação Sanguínea , Interleucina-17 , Interleucina-23 , Psoríase , Humanos , Psoríase/tratamento farmacológico , Psoríase/sangue , Psoríase/imunologia , Estudos Retrospectivos , Masculino , Interleucina-17/antagonistas & inibidores , Interleucina-17/sangue , Feminino , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais Humanizados/efeitos adversos , Pessoa de Meia-Idade , Interleucina-23/antagonistas & inibidores , Interleucina-23/sangue , Adulto , Coagulação Sanguínea/efeitos dos fármacos , Idoso , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais/efeitos adversosRESUMO
BACKGROUND: Abnormal biological behaviour of keratinocytes (KCs) is a critical pathophysiological manifestation of psoriasis. Ferroptosis is programmed cell death induced by the accumulation of lipid reactive oxygen species (ROS) in the presence of increased intracellular iron ions or inhibition of GPX4. OBJECTIVES: The purpose of this study was to investigate the effects of ferroptosis on the biological behaviour of Keratinocytes (KCs) in psoriasis vulgaris and its possible regulatory mechanisms in clinical samples, cells, and mouse models. METHODS: We first examined the differences in the expression of GPX4 and 4-HNE between psoriasis and normal human lesions. And detected KRT6, FLG, and inflammatory cytokines after inducing ferroptosis in animal and cell models by RT-qPCR, Western blot, immunohistochemistry, and flow cytometry. RESULTS: We found that GPX4 was decreased and that the oxidation product 4-hydroxy-2-nonenal (HNE) was increased in the skin lesions of patients with psoriasis vulgaris. The expression level of GPX4 correlates with the severity of skin lesions. Moreover, inducing ferroptosis promoted the expression of FLG and reduced the expression of KRT6 and inflammatory cytokines in vitro, and alleviated the phenotype of skin lesions in vivo. LIMITATIONS: Our study has limitations, notably small sample size. Larger clinical trials are necessary to investigate the association between ferroptosis and disease progression further. More research is necessary to explore how the ferroptosis inducer RSL3 regulates the abnormal biological behaviour of KCs at both cellular and animal levels and establish ferroptosis inhibitors as controls. CONCLUSIONS: This study confirms the existence of ferroptosis in psoriatic lesions, which may be inversely correlated with disease severity. The ferroptosis inducer RSL3 ameliorated psoriatic symptoms by improving the abnormal biological behaviour of KCs.
Assuntos
Modelos Animais de Doenças , Ferroptose , Queratinócitos , Fosfolipídeo Hidroperóxido Glutationa Peroxidase , Psoríase , Psoríase/patologia , Psoríase/metabolismo , Psoríase/imunologia , Ferroptose/fisiologia , Queratinócitos/metabolismo , Queratinócitos/patologia , Humanos , Animais , Camundongos , Projetos Piloto , Fosfolipídeo Hidroperóxido Glutationa Peroxidase/metabolismo , Fosfolipídeo Hidroperóxido Glutationa Peroxidase/genética , Aldeídos/metabolismo , Feminino , Masculino , Adulto , Queratina-6/metabolismo , Citocinas/metabolismo , Pele/patologia , Pele/metabolismo , Pele/imunologia , Pessoa de Meia-Idade , Resorcinóis/farmacologia , Espécies Reativas de Oxigênio/metabolismo , CarbolinasRESUMO
Two presentations at the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) 2023 annual meeting focused on unintended consequences of immunomodulatory therapy for psoriasis (PsO). Dr. Elizabeth Wallace presented on unintended consequences of tumor necrosis factor inhibitors for treating PsO and other inflammatory disorders. These consequences include paradoxical PsO, which is defined as unexpected new PsO cases or worsening PsO symptoms seemingly induced by treatment. Dr. Bruce Kirkham focused on unintended consequences of dupilumab treatment, which can include a musculoskeletal syndrome similar to psoriatic arthritis.
Assuntos
Anticorpos Monoclonais Humanizados , Doenças Musculoesqueléticas , Psoríase , Humanos , Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Monoclonais Humanizados/uso terapêutico , Psoríase/induzido quimicamente , Psoríase/tratamento farmacológico , Psoríase/imunologia , Doenças Musculoesqueléticas/induzido quimicamente , Doenças Musculoesqueléticas/imunologia , Artrite Psoriásica/tratamento farmacológico , Imunoterapia/efeitos adversos , Imunoterapia/métodosRESUMO
Psoriasis is a skin disease that is inflammatory and persistent, causing a high rate of recurrence, poor quality of life, and significant socioeconomic burden. Its main pathological manifestations are abnormal activation and infiltration of T cells and excessive proliferation of keratinocytes (KCs). The great majority of patients with psoriasis will relapse after remission. It usually lasts a lifetime and necessitates long-term treatment strategies. During periods of activity and remission, one of the main cell types in psoriasis is memory T cells, which include tissue-resident memory T (TRM) cells, central memory T (TCM) cells, and effector memory T (TEM) cells. They work by releasing inflammatory factors, cytotoxic particles, or altering cell subpopulations, leading to increased inflammation or recurrence. This review summarizes the role of memory T cells in the pathology and treatment of psoriasis, with a view to potential novel therapies and therapeutic targets.
Assuntos
Memória Imunológica , Células T de Memória , Psoríase , Psoríase/imunologia , Psoríase/terapia , Humanos , Células T de Memória/imunologia , Animais , Pele/imunologia , Pele/patologia , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo , Queratinócitos/imunologiaRESUMO
BACKGROUND: Retinol binding protein 4 (RBP4) is a mediator of inflammation and related to skin lesion formation, which suggests its engagement in psoriasis pathology and progression. This study intended to explore the change in RBP4 after systemic treatments, and its ability to predict treatment response in psoriasis patients. METHODS: This prospective study enrolled 85 psoriasis patients and 20 healthy subjects. Plasma RBP4 was detected by enzyme-linked immunosorbent assay at baseline and 12th week (W12) after systemic treatments in psoriasis patients, as well as after enrollment in healthy subjects. Psoriasis Area and Severity Index (PASI) 75 and PASI 90 were evaluated at W12 in psoriasis patients. RESULTS: RBP4 at baseline was higher in psoriasis patients than in healthy subjects [median (interquartile range): 13.39 (9.71-22.92) versus 9.59 (6.57-13.72) µg/mL] (P = 0.003). In psoriasis patients, 50 (58.8%) patients achieved PASI 75 at W12, and 25 (29.4%) patients achieved PASI 90 at W12. RBP4 was decreased at W12 compared to its level at baseline (P < 0.001). Lower RBP4 at baseline predicted achieving PASI 75 at W12 (P = 0.038). Greater RBP4 change (baseline-W12) precited achieving PASI 75 (P = 0.036) and PASI 90 (P = 0.045) at W12. Receiver operating characteristic curves suggested that after adjustment for all clinical features, RBP4 at baseline and RBP4 change (baseline-W12) had an acceptable ability to predict PASI 75 and PASI 90 at W12 with all area under curve values > 0.7. CONCLUSION: Plasma RBP4 is decreased after systemic treatments, and its low baseline level and greater decline after treatments predict good treatment response in psoriasis patients.
Assuntos
Psoríase , Proteínas Plasmáticas de Ligação ao Retinol , Humanos , Psoríase/tratamento farmacológico , Psoríase/sangue , Psoríase/imunologia , Proteínas Plasmáticas de Ligação ao Retinol/metabolismo , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Estudos Prospectivos , Resultado do Tratamento , Biomarcadores/sangue , Índice de Gravidade de Doença , Curva ROCRESUMO
Bruton's tyrosine kinase (BTK), a nonreceptor tyrosine kinase, plays a remarkable role in the transmission and amplification of extracellular signals to intracellular signaling pathways. Various types of cells use the BTK pathway to communicate, including hematopoietic cells particularly B cells and T cells. The BTK pathway plays a role in controlling the proliferation, survival, and functions of B cells as well as other myeloid cells. First, second, and third-generation BTK inhibitors are currently being evaluated for the treatment of immune-mediated diseases in addition to B cell malignancies. In this article, the available evidence on the action mechanisms of BTK inhibitors is reviewed. Then, the most recent data obtained from preclinical studies and ongoing clinical trials for the treatment of autoimmune diseases, such as pemphigus vulgaris, pemphigus foliaceus, bullous pemphigoid, systemic lupus erythematosus, Sjögren's disease, rheumatoid arthritis, systemic sclerosis, multiple sclerosis, myasthenia gravis, and inflammatory diseases such as psoriasis, chronic spontaneous urticaria, atopic dermatitis, and asthma are discussed. In addition, adverse effects and complications associated with BTK inhibitors as well as factors predisposing patients to BTK inhibitors complications are discussed.
Assuntos
Tirosina Quinase da Agamaglobulinemia , Doenças Autoimunes , Pênfigo , Inibidores de Proteínas Quinases , Transdução de Sinais , Humanos , Tirosina Quinase da Agamaglobulinemia/antagonistas & inibidores , Doenças Autoimunes/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico , Pênfigo/tratamento farmacológico , Pênfigo/imunologia , Pirimidinas/uso terapêutico , Piperidinas/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/imunologia , Miastenia Gravis/tratamento farmacológico , Esclerose Múltipla/tratamento farmacológico , Pirazóis/uso terapêutico , Pirazóis/farmacologia , Nitrilas/uso terapêutico , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Lúpus Eritematoso Sistêmico/imunologia , Adenina/análogos & derivados , Adenina/uso terapêutico , Asma/tratamento farmacológico , Linfócitos B/imunologia , Síndrome de Sjogren/tratamento farmacológico , Psoríase/tratamento farmacológico , Psoríase/imunologia , Escleroderma Sistêmico/tratamento farmacológico , Proteínas Tirosina Quinases/antagonistas & inibidores , Benzamidas , Imidazóis , PirazinasRESUMO
Despite recent advancements in psoriasis treatment, challenges in management persist. Recently, there has been a rising interest amongst patients in complementary and alternative medicines (CAM), driven by the desire for more natural, holistic approaches and dissatisfaction with conventional treatments. Up to 41% of patients with psoriasis reported using alternative therapies and 39.5% use complementary therapies (Murphy EC, Nussbaum D, Prussick R, Friedman AJ (2019) Use of complementary and alternative medicine by patients with psoriasis. J Am Acad Dermatol 81:280-283). Despite their rapidly growing prevalence, literature on CAM therapies for psoriasis is lacking, making their recommendation difficult. Since the last systematic review on this topic published in 2018, evidence for new alternative therapies has emerged, promoting a further investigation of their efficacy (Gamret AC, Price A, Fertig RM, Lev-Tov H, Nichols AJ (2018) Complementary and Alternative Medicine Therapies for Psoriasis: A Systematic Review. JAMA Dermatol 154:1330-1337). This systematic review aims to compile recent literature on the most studied alternative therapies for psoriasis and further discuss their effectiveness in order to counsel clinicians in guiding patients on the use of these non-standard approaches. A literature search was conducted in the PubMed, EMBASE, Cochrane Central Register of Controlled Trials, and Clinicaltrials.gov databases for randomized controlled trials (RCT) on complementary and alternative therapies in psoriasis from March 2018 through April 2024, resulting in 12 studies being included in this review. The preliminary results for many treatments such as curcumin, dietary modification and additions, indigo naturalis, meditation, acupuncture, and balneotherapy showed positive clinical effects. However, additional well-designed randomized trials are needed to confirm the potential beneficial effects and to establish safety of use.
Assuntos
Terapias Complementares , Psoríase , Humanos , Psoríase/terapia , Psoríase/imunologia , Terapias Complementares/métodos , Resultado do Tratamento , Ensaios Clínicos Controlados Aleatórios como Assunto , Terapia por Acupuntura/métodosRESUMO
Generalized pustular psoriasis (GPP) is a rare but severe form of psoriasis. However, the pathogenesis of GPP has not been fully elucidated. Although RNA-binding proteins (RBPs) and the alternative splicing (AS) process are essential for regulating post-transcriptional gene expression, their roles in GPP are still unclear. We aimed to elucidate the regulatory mechanisms to identify potential new therapeutic targets. Here, We analyzed an RNA sequencing (RNA-seq) dataset (GSE200977) of peripheral blood mononuclear cells (PBMCs) of 24 patients with GPP, psoriasis vulgaris (PV), and healthy controls (HCs) from the Gene Expression Omnibus (GEO) database. We found that the abnormal alternative splicing (AS) events associated with GPP were mainly "alt3p/alt5p", and 15 AS genes were differentially expressed. Notably, the proportions of different immune cell types were correlated with the expression levels of regulatory alternatively spliced genes (RASGs): significant differences were observed in expression levels of DTD2, NDUFAF3, NBPF15, and FBLN7 in B cells and ARFIP1, IPO11, and RP11-326L24.9 in neutrophils in the GPP samples. Furthermore, We identified 32 differentially expressed RNA-binding proteins (RBPs) (18 up-regulated and 14 down-regulated). Co-expression networks between 14 pairs of differentially expressed RBPs and RASGs were subsequently constructed, demonstrating that these differentially expressed RBPs may affect the progression of GPP by regulating the AS of downstream immune/inflammatory-related genes such as LINC00989, ENC1 and MMP25-AS1. Our results were innovative in revealing the involvement of inflammation-related RBPs and RASGs in the development of GPP from the perspective of RBP-regulated AS.
Assuntos
Processamento Alternativo , Progressão da Doença , Psoríase , Proteínas de Ligação a RNA , Humanos , Psoríase/genética , Psoríase/imunologia , Psoríase/patologia , Processamento Alternativo/genética , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo , Masculino , Feminino , Leucócitos Mononucleares/metabolismo , Leucócitos Mononucleares/imunologia , Perfilação da Expressão Gênica , Adulto , Pessoa de Meia-Idade , Estudos de Casos e ControlesRESUMO
NETosis, a regulated form of neutrophil death, is crucial for host defense against pathogens. However, the release of neutrophil extracellular traps (NETs) during NETosis can have detrimental effects on surrounding tissues and contribute to the pro-inflammatory response, in addition to their role in controlling microbes. Although it is well-established that the IL-23-Th17 axis plays a key role in the pathogenesis of psoriasis, emerging evidence suggests that psoriasis, as an autoinflammatory disease, is also associated with NETosis. The purpose of this review is to provide a comprehensive understanding of the mechanisms underlying NETosis in psoriasis. It will cover topics such as the formation of NETs, immune cells involved in NETosis, and potential biomarkers as prognostic/predicting factors in psoriasis. By analyzing the intricate relationship between NETosis and psoriasis, this review also aims to identify novel possibilities targeting NETosis for the treatment of psoriasis.
Assuntos
Armadilhas Extracelulares , Inflamação , Neutrófilos , Psoríase , Psoríase/imunologia , Humanos , Armadilhas Extracelulares/imunologia , Armadilhas Extracelulares/metabolismo , Neutrófilos/imunologia , Neutrófilos/metabolismo , Animais , Inflamação/imunologia , BiomarcadoresRESUMO
Psoriasis is an autoinflammatory dermatosis, while methotrexate (MTX) is an immunosuppressant used to treat psoriasis. However, conventional immunosuppressants may cause various side effects. Acupuncture has potential benefits in treating psoriasis based on its anti-inflammatory effects. However, the immune mechanisms underlying its effects remain unclear. In this study, imiquimod-induced psoriatic mice were used to investigate the effects and mechanisms of electroacupuncture (EA) and, in particular, its joint treatment with MTX. We found that treatment with either EA or MTX ameliorated psoriasiform skin lesions, improved skin pathology and reduced proinflammatory cytokines in the skin, while joint treatment with both EA and MTX further alleviated the skin lesions and inflammation compared to either one alone. Moreover, percentages of CD4+ IL-17A+ Th17 cells in the skin and lymph nodes were decreased by EA or MTX and further lowered by combined EA+MTX treatment. Similarly, EA or MTX also reduced their RORγt expression. On the contrary, CD4+ FoxP3+ Treg frequency in psoriatic mice was augmented by EA or MTX and further increased by the joint treatment. However, depleting Tregs mostly reversed the therapeutic effects of EA or EA plus MTX. Additionally, the phosphorylated NF-κB (p65) expression was suppressed by treatment with EA, MTX or better with EA+MTX. Meanwhile, the anti-inflammatory effects of EA plus MTX were offset by an NF-κB agonist. Thus, this study has revealed that EA cooperates with MTX to balance Th17/Treg responses and to ameliorate psoriasiform skin inflammation through suppressing NF-κB activation. Our findings may be implicated for treating human psoriasis.
Assuntos
Eletroacupuntura , Imiquimode , Metotrexato , Psoríase , Pele , Linfócitos T Reguladores , Células Th17 , Animais , Psoríase/imunologia , Psoríase/tratamento farmacológico , Psoríase/terapia , Psoríase/induzido quimicamente , Células Th17/imunologia , Células Th17/efeitos dos fármacos , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/efeitos dos fármacos , Eletroacupuntura/métodos , Pele/patologia , Pele/efeitos dos fármacos , Pele/imunologia , Camundongos , Modelos Animais de Doenças , Citocinas/metabolismo , Camundongos Endogâmicos C57BL , Humanos , NF-kappa B/metabolismo , Terapia Combinada , Masculino , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares/metabolismoRESUMO
Atopic dermatitis (AD) and psoriasis are chronic skin diseases with a global impact, posing significant challenges to public health systems and severely affecting patients' quality of life. This review delves into the key role of the gut microbiota in these diseases, emphasizing the importance of the gut-skin axis in inflammatory mediators and immune regulation and revealing a complex bidirectional communication system. We comprehensively assessed the pathogenesis, clinical manifestations, and treatment strategies for AD and psoriasis, with a particular focus on how the gut microbiota and their metabolites influence disease progression via the gut-skin axis. In addition, personalized treatment plans based on individual patient microbiome characteristics have been proposed, offering new perspectives for future treatment approaches. We call for enhanced interdisciplinary cooperation to further explore the interactions between gut microbiota and skin diseases and to assess the potential of drugs and natural products in modulating the gut-skin axis, aiming to advance the treatment of skin diseases.
Assuntos
Dermatite Atópica , Microbioma Gastrointestinal , Psoríase , Pele , Humanos , Dermatite Atópica/imunologia , Dermatite Atópica/microbiologia , Psoríase/imunologia , Psoríase/microbiologia , Microbioma Gastrointestinal/imunologia , Pele/microbiologia , Pele/imunologia , Pele/patologia , AnimaisRESUMO
Psoriasis is a prevalent chronic inflammatory and immunological disorder. Its lesions are present as scaly erythema or plaques. Disruptions in the body's immune system play a significant role in developing psoriasis. Recent evidence suggests a potential role of the gut microbiome in autoimmune diseases. Short-chain fatty acids (SCFAs) are the primary metabolites created by gut microbes and play a crucial fuction in autoimmunity. SCFAs act on various cells by mediating signaling to participate in host physiological and pathological processes. These processes encompass body metabolism, maintenance of intestinal barrier function, and immune system modulation. SCFAs can regulate immune cells to enhance the body's immune function, potentially influencing the prevention and treatment of psoriasis. However, the mechanisms underlying the role of SCFAs in psoriasis remain incompletely understood. This paper examines the relationship between SCFAs and psoriasis, elucidating how SCFAs influence the immune system, inflammatory response, and gut barrier in psoriasis. According to the study, in psoriasis, SCFAs have been shown to regulate neutrophils, macrophages, and dendritic cells in the adaptive immune system, as well as T and B cells in the innate immune system. Additionally, we explore the role of SCFAs in psoriasis by maintaining intestinal barrier function, restoring intestinal ecological homeostasis, and investigating the potential therapeutic benefits of SCFAs for psoriasis.
Assuntos
Ácidos Graxos Voláteis , Microbioma Gastrointestinal , Psoríase , Psoríase/imunologia , Psoríase/tratamento farmacológico , Psoríase/metabolismo , Humanos , Ácidos Graxos Voláteis/metabolismo , Ácidos Graxos Voláteis/uso terapêutico , Animais , Microbioma Gastrointestinal/imunologia , Imunidade InataRESUMO
Psoriasis is a chronic condition caused by an inflammation mediated mainly by cytokines and T cells. In COVID-19, the same type of imbalance is common, generating the Cytokine Storm and promoting a worsening in the skin conditions of patients with autoimmune disorders, such as Psoriasis. In this context, one of the main mediators of immune responses presented by SARS-CoV-2 infected patients is the Purinergic System. This immunological resource is capable of stimulating the hyperinflammatory state presented by infected individuals, mainly by the activity of the P2X7 receptor, culminating in the Cytokine Storm and consequently in the Psoriasis crisis. Currently, different drugs are used for patients with Psoriasis, such as immunosuppressants and small molecules; however, the safety of these drugs in infected patients has not been analyzed yet. In this context, studies are being developed to evaluate the possible administration of these traditional drugs to COVID-19 patients with Psoriasis crisis. Along with that, researchers must evaluate the potential of administrating P2X7 antagonists to these patients as well, improving both the systemic and the dermatological prognostics of patients, by reducing the Cytokine Storm and its general effects, but also avoiding the provocation of Psoriasis crisis.
Assuntos
COVID-19 , Síndrome da Liberação de Citocina , Psoríase , SARS-CoV-2 , Humanos , Psoríase/imunologia , Psoríase/tratamento farmacológico , COVID-19/imunologia , COVID-19/complicações , Síndrome da Liberação de Citocina/imunologia , Síndrome da Liberação de Citocina/etiologia , Síndrome da Liberação de Citocina/tratamento farmacológico , SARS-CoV-2/imunologia , Imunomodulação/efeitos dos fármacos , Imunossupressores/uso terapêutico , Receptores Purinérgicos P2X7/metabolismo , Citocinas/metabolismo , Citocinas/imunologia , Antagonistas do Receptor Purinérgico P2X/uso terapêuticoRESUMO
Psoriasis is a chronic inflammatory skin disease occurring worldwide. Initially viewed as a keratinocyte disorder, psoriasis is now recognized to involve a complex interplay between genetic predisposition, environmental triggers, and a dysregulated immune system, with a significant role of CD4+ T cells producing IL-17. Recent genetic studies have identified susceptibility loci that underscore the importance of innate immune responses, particularly the roles of myeloid cells, such as dendritic cells, macrophages, and neutrophils. These cells initiate and sustain inflammation through cytokine production triggered by external stimuli. They influence keratinocyte behavior and interact with adaptive immune cells. Recent techniques have further revealed the heterogeneity of myeloid cells in psoriatic lesions, highlighting the contributions of less-studied subsets, such as eosinophils and mast cells. This review examines the multifaceted roles of myeloid innate immune cells in psoriasis, emphasizing their functional diversity in promoting psoriatic inflammation. It also describes current treatment targeting myeloid innate immune cells and explores potential new therapeutic strategies based on the functional characteristics of these subsets. Future research should focus on the detailed characterization of myeloid subsets and their interactions to develop targeted treatments that address the complex immune landscape of psoriasis.