RESUMEN
Infectious, inflammatory and autoimmune conditions present differently in males and females. SARS-CoV-2 infection in naive males is associated with increased risk of death, whereas females are at increased risk of long COVID1, similar to observations in other infections2. Females respond more strongly to vaccines, and adverse reactions are more frequent3, like most autoimmune diseases4. Immunological sex differences stem from genetic, hormonal and behavioural factors5 but their relative importance is only partially understood6-8. In individuals assigned female sex at birth and undergoing gender-affirming testosterone therapy (trans men), hormone concentrations change markedly but the immunological consequences are poorly understood. Here we performed longitudinal systems-level analyses in 23 trans men and found that testosterone modulates a cross-regulated axis between type-I interferon and tumour necrosis factor. This is mediated by functional attenuation of type-I interferon responses in both plasmacytoid dendritic cells and monocytes. Conversely, testosterone potentiates monocyte responses leading to increased tumour necrosis factor, interleukin-6 and interleukin-15 production and downstream activation of nuclear factor kappa B-regulated genes and potentiation of interferon-γ responses, primarily in natural killer cells. These findings in trans men are corroborated by sex-divergent responses in public datasets and illustrate the dynamic regulation of human immunity by sex hormones, with implications for the health of individuals undergoing hormone therapy and our understanding of sex-divergent immune responses in cisgender individuals.
Asunto(s)
Testosterona , Personas Transgénero , Adulto , Femenino , Humanos , Masculino , Conjuntos de Datos como Asunto , Células Dendríticas/inmunología , Células Dendríticas/metabolismo , Células Dendríticas/efectos de los fármacos , Sistema Inmunológico/efectos de los fármacos , Sistema Inmunológico/metabolismo , Interferón Tipo I/inmunología , Interferón Tipo I/metabolismo , Interferón gamma/inmunología , Interferón gamma/metabolismo , Interleucina-15/inmunología , Interleucina-15/metabolismo , Células Asesinas Naturales/inmunología , Células Asesinas Naturales/efectos de los fármacos , Monocitos/inmunología , Monocitos/efectos de los fármacos , Monocitos/metabolismo , FN-kappa B/metabolismo , Caracteres Sexuales , Testosterona/efectos adversos , Testosterona/inmunología , Testosterona/farmacología , Testosterona/uso terapéutico , Factor de Necrosis Tumoral alfa/metabolismoAsunto(s)
Sistema Endocrino , Humanos , Animales , Sistema Endocrino/fisiología , Sistema InmunológicoRESUMEN
The intricate interplay between Homeobox genes, long non-coding RNAs (lncRNAs), and the development of malignancies represents a rapidly expanding area of research. Specific discernible lncRNAs have been discovered to adeptly regulate HOX gene expression in the context of cancer, providing fresh insights into the molecular mechanisms that govern cancer development and progression. An in-depth comprehension of these intricate associations may pave the way for innovative therapeutic strategies in cancer treatment. The HOX gene family is garnering increasing attention due to its involvement in immune system regulation, interaction with long non-coding RNAs, and tumor progression. Although initially recognized for its crucial role in embryonic development, this comprehensive exploration of the world of HOX genes contributes to our understanding of their diverse functions, potentially leading to immunology, developmental biology, and cancer research discoveries. Thus, the primary objective of this review is to delve into these aspects of HOX gene biology in greater detail, shedding light on their complex functions and potential therapeutic applications.
Asunto(s)
Progresión de la Enfermedad , Regulación Neoplásica de la Expresión Génica , Genes Homeobox , Sistema Inmunológico , Neoplasias , ARN Largo no Codificante , Humanos , Neoplasias/genética , Neoplasias/inmunología , ARN Largo no Codificante/genética , Genes Homeobox/genética , Sistema Inmunológico/metabolismo , AnimalesRESUMEN
It is well known that during prolonged, high-intensity physical training, athletes experience a state of immunosuppression and that balanced nutrition can help maintain immunity. This review summarizes the effects (amplified by virus infection) of high-intensity, long-term exercise on immunity, critically presenting key micronutrients and supplementation strategies that can influence athletes' performance and their immune system. The main conclusion is that micronutrient supplementation with diet could help to protect the immune system from the stress effects induced by intense physical activities. The importance of personalized supplementation has been also recommended.
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Suplementos Dietéticos , Sistema Inmunológico , Micronutrientes , Humanos , Micronutrientes/administración & dosificación , Sistema Inmunológico/efectos de los fármacos , Ejercicio Físico/fisiología , Atletas , Rendimiento Atlético/fisiología , Entrenamiento de Intervalos de Alta Intensidad/métodosRESUMEN
Liver failure profoundly affects the immune system, leading to dysregulation of innate and adaptive immune response. This review explores the intricate relationship between liver function and immune homeostasis. The role of the liver as a central hub in immune response initiation is elucidated, emphasizing its involvement in hepatic inflammation induction and subsequent systemic inflammation. Cytokines, chemokines, growth factors, and lipid mediators orchestrate these immune processes, serving as both prognostic biomarkers and potential therapeutic targets in liver failure-associated immune dysregulation, which might result from acute-on-chronic liver failure (ACLF) and cirrhosis. Furthermore, the review delves into the mechanisms underlying immunosuppression in liver failure, encompassing alterations in innate immune cell functions such as neutrophils, macrophages, and natural killer cells (NK cells), as well as perturbations in adaptive immune responses mediated by B and T cells. Conclusion: Understanding the immunological consequences of liver failure is crucial for developing targeted therapeutic interventions and improving patient outcomes in liver disease management.
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Inmunidad Innata , Fallo Hepático , Humanos , Fallo Hepático/inmunología , Animales , Sistema Inmunológico/metabolismo , Sistema Inmunológico/inmunología , Inmunidad Adaptativa , Células Asesinas Naturales/inmunología , Citocinas/metabolismo , Hígado/inmunología , Hígado/metabolismo , Hígado/patologíaRESUMEN
The immune system has a vital, albeit complex, relationship with the microbes residing within us, one that we are only beginning to understand. We asked investigators what they felt were the fundamental challenges we currently face in unraveling the impacts of microbes and their metabolites on host immunity and to discuss key opportunities toward achieving future insights and innovation.
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Inmunidad , Humanos , Animales , Microbiota/inmunología , Interacciones Huésped-Patógeno/inmunología , Sistema Inmunológico/inmunología , Sistema Inmunológico/metabolismo , Bacterias/inmunología , Bacterias/metabolismoAsunto(s)
Sistema Inmunológico , Procedimientos de Reasignación de Sexo , Testosterona , Personas Transgénero , Femenino , Humanos , Masculino , Sistema Inmunológico/efectos de los fármacos , Sistema Inmunológico/inmunología , Testosterona/efectos adversos , Testosterona/farmacología , Testosterona/uso terapéuticoRESUMEN
Focused ultrasound is a platform technology capable of eliciting a wide range of biological responses with high spatial precision deep within the body. Although focused ultrasound is already in clinical use for focal thermal ablation of tissue, there has been a recent growth in development and translation of ultrasound-mediated nonthermal therapies. These approaches exploit the physical forces of ultrasound to produce a range of biological responses dependent on exposure conditions. This review discusses recent advances in four application areas that have seen particular growth and have immense clinical potential: brain drug delivery, neuromodulation, focal tissue destruction, and endogenous immune system activation. Owing to the maturation of transcranial ultrasound technology, the brain is a major target organ; however, clinical indications outside the brain are also discussed.
Asunto(s)
Encéfalo , Sistemas de Liberación de Medicamentos , Ultrasonido Enfocado de Alta Intensidad de Ablación , Animales , Humanos , Encéfalo/diagnóstico por imagen , Ultrasonido Enfocado de Alta Intensidad de Ablación/métodos , Sistema InmunológicoRESUMEN
The role of immune system components in the development of myocardial remodeling in chronic kidney disease (CKD) and kidney transplantation remains an open question. Our aim was to investigate the associations between immune cell subpopulations in the circulation of CKD patients and kidney transplant recipients (KTRs) with subclinical indices of myocardial performance. We enrolled 44 CKD patients and 38 KTRs without established cardiovascular disease. A selected panel of immune cells was measured by flow cytometry. Classical and novel strain-related indices of ventricular function were measured by speckle-tracking echocardiography at baseline and following dipyridamole infusion. In CKD patients, the left ventricular (LV) relative wall thickness correlated with the CD14++CD16- monocytes (ß = 0.447, p = 0.004), while the CD14++CD16+ monocytes were independent correlates of the global radial strain (ß = 0.351, p = 0.04). In KTRs, dipyridamole induced changes in global longitudinal strain correlated with CD14++CD16+ monocytes (ß = 0.423, p = 0.009) and CD4+ T-cells (ß = 0.403, p = 0.01). LV twist and untwist were independently correlated with the CD8+ T-cells (ß = 0.405, p = 0.02 and ß = -0.367, p = 0.03, respectively) in CKD patients, whereas the CD14++CD16+ monocytes were independent correlates of LV twist and untwist in KTRs (ß = 0.405, p = 0.02 and ß = -0.367, p = 0.03, respectively). Immune cell subsets independently correlate with left ventricular strain and torsion-related indices in CKD patients and KTRs without established CVD.
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Trasplante de Riñón , Monocitos , Insuficiencia Renal Crónica , Humanos , Trasplante de Riñón/efectos adversos , Masculino , Femenino , Insuficiencia Renal Crónica/inmunología , Persona de Mediana Edad , Monocitos/metabolismo , Monocitos/inmunología , Ecocardiografía , Adulto , Receptores de Lipopolisacáridos/metabolismo , Enfermedades Cardiovasculares/etiología , Anciano , Receptores de Trasplantes , Sistema Inmunológico , Receptores de IgG/metabolismoRESUMEN
Ageing as a natural irreversible process inherently results in the functional deterioration of numerous organ systems and tissues, including the skeletal and immune systems. Recent studies have elucidated the intricate bidirectional interactions between these two systems. In this review, we provide a comprehensive synthesis of molecular mechanisms of cell ageing. We further discuss how age-related skeletal changes influence the immune system and the consequent impact of immune system alterations on the skeletal system. Finally, we highlight the clinical implications of these findings and propose potential strategies to promote healthy ageing and reduce pathologic deterioration of both the skeletal and immune systems.
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Envejecimiento , Huesos , Sistema Inmunológico , Humanos , Envejecimiento/inmunología , Envejecimiento/fisiología , Sistema Inmunológico/inmunología , Sistema Inmunológico/fisiología , Huesos/inmunología , AnimalesRESUMEN
Mother and child are immunologically interconnected by mechanisms that we are only beginning to understand. During pregnancy, multiple molecular and cellular factors of maternal origin are transferred across the placenta and influence the development and function of the fetal and newborn immune system. Altered maternal immune states arising from pregnancy-associated infections or immunizations have the potential to program offspring immune function in ways that may have long-term health consequences. In this study, we review current literature on the impact of prenatal infection and vaccination on the developing immune system, highlight knowledge gaps, and look to the horizon to envision maternal interventions that could benefit both the mother and her child.
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Vacunación , Humanos , Embarazo , Femenino , Recién Nacido , Placenta/inmunología , Sistema Inmunológico/inmunología , Complicaciones Infecciosas del Embarazo/inmunología , Intercambio Materno-Fetal/inmunología , Madres , Niño , Feto/inmunología , Efectos Tardíos de la Exposición Prenatal/inmunologíaRESUMEN
Historically, amphibians have been essential to our understanding of vertebrate biology and animal development. Because development from egg to tadpole to adult frog can be directly observed, amphibians contributed greatly to our understanding of not only vertebrate animal development but also the development of the immune system. The South African clawed frog (Xenopus laevis) has been key to many of these findings. For example, using Xenopus as a model, the comparative immunology community learned about the contribution of hematopoietic stem cells to development of the immune system and about the diversity of antibodies, B cells, T cells and antigen presenting cells. Amphibians offer many advantages as unique potential model systems to address questions about immune skin interactions, host responses to mycobacteria, the diverse functions of interferons, and immune and mucosal interactions. However, there are also many challenges to advance the research including the lack of specific reagents and well annotated genomes of diverse species. While much is known, many important questions remain. The aim of this short commentary is to look to the future of comparative immunology of amphibians as a group. By identifying some important questions or "information-deficit" areas of research, I hope to pique the interest of younger developing scientists and persuade funding agencies to continue to support comparative immunology studies including those of amphibians.
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Anfibios , Animales , Anfibios/inmunología , Alergia e Inmunología , Sistema Inmunológico/inmunología , Xenopus laevis/inmunologíaRESUMEN
Climate change associated with human activities alters marine ecosystems and causes imbalances and abrupt changes in sea conditions. Scarce freshwater resources for human consumption often prompt the construction of desalination plants, which discharge significant amounts of brine into the sea, potentially elevating salinity levels. Furthermore, global trade together with higher temperature and pollution can facilitate the spread of parasites. The aim of this study was to assess the potential effects of salinity, an abiotic stressor, and Scaphanocephalus sp. parasitic infection responsible for black spot disease, a biotic stressor, on Coris julis, a common fish in the Balearic Islands (Spain). Fish were sampled from an area affected by a desalination plant, one with a high rate of parasite infection and a control area, and biomarkers were analysed in the liver, gills and epithelial mucosa. Both salinity and the parasite induced increases in catalase (CAT) and glutathione s-transferase activities in the liver, while superoxide dismutase (SOD) did not show significant changes. The effects of salinity were evident to a greater extent in the gills with an increase in the activity of all enzymes, as well as in the production of reactive species. The effects of the parasite were mainly observed in the mucus with significant increases in CAT and SOD activities. Regarding immune response markers in the mucus, both stressors induced an increase in lysozyme and alkaline phosphatase activities, and in the case of the parasite, also an increase in immunoglobulins. Malondialdehyde, as an indicator of oxidative damage, remained unchanged. In conclusion, both abiotic and abiotic stress induce a stress situation in C. julis that responds by activating its antioxidant and immune defence mechanisms but does cause oxidative damage. The differential tissue response to different stressors highlights the value of analysing multiple tissues to detect early indicators of diverse impacts on marine fauna.
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Antioxidantes , Salinidad , España , Animales , Antioxidantes/metabolismo , Enfermedades de los Peces/parasitología , Sistema Inmunológico , Branquias/parasitología , Monitoreo del AmbienteRESUMEN
Human immune system (HIS) mice generated using human CD34+ hematopoietic stem cells serve as a pivotal model for the in vivo evaluation of immunotherapies for humans. Yet, HIS mice possess certain limitations. Rats, due to their size and comprehensive immune system, hold promise for translational experiments. Here, we describe an efficacious method for long-term immune humanization, through intrahepatic injection of hCD34+ cells in newborn immunodeficient rats expressing human SIRPα. In contrast to HIS mice and similar to humans, HIS rats showed in blood a predominance of T cells, followed by B cells. Immune humanization was also high in central and secondary lymphoid organs. HIS rats treated with the anti-human CD3 antibody were depleted of human T cells, and human cytokines were detected in sera. We describe for the first time a method to efficiently generate HIS rats. HIS rats have the potential to be a useful model for translational immunology.
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Antígenos CD34 , Animales , Humanos , Antígenos CD34/metabolismo , Ratas , Células Madre Hematopoyéticas/citología , Células Madre Hematopoyéticas/metabolismo , Células Madre Hematopoyéticas/inmunología , Linfocitos T/inmunología , Linfocitos T/metabolismo , Receptores Inmunológicos/metabolismo , Receptores Inmunológicos/inmunología , Receptores Inmunológicos/genética , Sistema Inmunológico/metabolismo , Citocinas/metabolismo , Linfocitos B/inmunología , Linfocitos B/metabolismo , Linfocitos B/citología , Trasplante de Células Madre Hematopoyéticas/métodos , Ratones , Antígenos de DiferenciaciónRESUMEN
Viral infections significantly impact the immune system, and impact will persist until recovery. However, the influence of severe acute respiratory syndrome coronavirus 2 infection on the homeostatic immune status and secondary immune response in recovered patients remains unclear. To investigate these persistent alterations, we employed five feature-ranking algorithms (LASSO, MCFS, RF, CATBoost, and XGBoost), incremental feature selection, synthetic minority oversampling technique and two classification algorithms (decision tree and k-nearest neighbors) to analyze multi-omics data (surface proteins and transcriptome) from coronavirus disease 2019 (COVID-19) recovered patients and healthy controls post-influenza vaccination. The single-cell multi-omics dataset was divided into five subsets corresponding to five immune cell subtypes: B cells, CD4+ T cells, CD8+ T cells, Monocytes, and Natural Killer cells. Each cell was represented by 28,402 scRNA-seq (RNA) features, 3 Hash Tag Oligo (HTO) features, 138 Cellular indexing of transcriptomes and epitopes by sequencing (CITE) features and 23,569 Single Cell Transform (SCT) features. Some multi-omics markers were identified and effective classifiers were constructed. Our findings indicate a distinct immune status in COVID-19 recovered patients, characterized by low expression of ribosomal protein (RPS26) and high expression of immune cell surface proteins (CD33, CD48). Notably, TMEM176B, a membrane protein, was highly expressed in monocytes of COVID-19 convalescent patients. These observations aid in discerning molecular differences among immune cell subtypes and contribute to understanding the prolonged effects of COVID-19 on the immune system, which is valuable for treating infectious diseases like COVID-19.
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COVID-19 , Aprendizaje Automático , SARS-CoV-2 , Análisis de la Célula Individual , Transcriptoma , COVID-19/inmunología , Humanos , SARS-CoV-2/inmunología , SARS-CoV-2/genética , Algoritmos , Sistema Inmunológico/inmunología , Linfocitos T CD8-positivos/inmunología , Vacunas contra la Influenza/inmunología , MultiómicaRESUMEN
The immune system is a major regulatory system of the body, that is composed of immune cells, immune organs, and related signaling factors. As an organism ages, observable age-related changes in the function of the immune system accumulate in a process described as 'immune aging. Research has shown that the impact of aging on immunity is detrimental, with various dysregulated responses that affect the function of immune cells at the cellular level. For example, increased aging has been shown to result in the abnormal chemotaxis of neutrophils and decreased phagocytosis of macrophages. Age-related diminished functionality of immune cell types has direct effects on host fitness, leading to poorer responses to vaccination, more inflammation and tissue damage, as well as autoimmune disorders and the inability to control infections. Similarly, age impacts the function of the immune system at the organ level, resulting in decreased hematopoietic function in the bone marrow, a gradual deficiency of catalase in the thymus, and thymic atrophy, resulting in reduced production of related immune cells such as B cells and T cells, further increasing the risk of autoimmune disorders in the elderly. As the immune function of the body weakens, aging cells and inflammatory factors cannot be cleared, resulting in a cycle of increased inflammation that accumulates over time. Cumulatively, the consequences of immune aging increase the likelihood of developing age-related diseases, such as Alzheimer's disease, atherosclerosis, and osteoporosis, among others. Therefore, targeting the age-related changes that occur within cells of the immune system might be an effective anti-aging strategy. In this article, we summarize the relevant literature on immune aging research, focusing on its impact on aging, in hopes of providing new directions for anti-aging research.
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Envejecimiento , Inmunosenescencia , Humanos , Animales , Envejecimiento/inmunología , Sistema Inmunológico/inmunología , Enfermedades Autoinmunes/inmunología , Inflamación/inmunologíaRESUMEN
The triadic interplay between sleep, immunity, and cancer represents a growing area of biomedical research with significant clinical implications. This review synthesizes the current knowledge on how sleep influences immune function, the immune system's role in cancer dynamics, and the direct connections between sleep patterns and cancer risk. After a comprehensive overview of the interrelationships among these three domains, the mechanisms of sleep in immune function are described, detailing how sleep regulates the immune system, the effects of sleep duration and quality on immune responses, and the underlying molecular and cellular mechanisms. Also, the complex relationship between immunity and cancer is explored, highlighting the immune system's role in cancer prevention and progression, immune surveillance, tumor microenvironment, and the implications of immunodeficiency and immune modulation on cancer risk. The direct connections between sleep and cancer are then described, presenting epidemiological evidence linking sleep patterns to cancer risk, biological mechanisms that influence cancer development, and the role of sleep disorders in cancer prognosis. The mediating role of sleep between immunity and cancer is highlighted, proposing hypothesized pathways, summarizing evidence from experimental and clinical studies, and evaluating the impact of sleep interventions on immune function and cancer outcomes. This review concludes by discussing the clinical implications and future directions, emphasizing the potential for sleep-based interventions in cancer prevention and treatment, the integration of sleep management in oncology and immunotherapy, and outlining a future research agenda. This agenda includes understanding the mechanisms of the sleep-immunity-cancer interplay, conducting epidemiological studies on sleep and cancer risk, assessing the impact of sleep management in cancer treatment protocols, exploring sleep and tumor microenvironment interactions, and considering policy and public health implications. Through a detailed examination of these interconnected pathways, this review underscores the critical importance of sleep in modulating immune function and cancer outcomes, advocating for interdisciplinary research and clinical strategies to harness this knowledge for improved health outcomes.