Sex bias in CNS autoimmune disease mediated by androgen control of autoimmune regulator
| العنوان: | Sex bias in CNS autoimmune disease mediated by androgen control of autoimmune regulator |
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| المؤلفون: | Jennifer S. Nelson, Joshua Starmer, Aaron D. Martin, Maureen A. Su, Meng-Lei Zhu, Bridget Conley, Elizabeth M. Wilson, Pearl Bakhru, Meghan E. Free |
| المصدر: | Nature Communications, Vol 7, Iss 1, Pp 1-14 (2016) Nature Communications |
| بيانات النشر: | Nature Portfolio, 2016. |
| سنة النشر: | 2016 |
| مصطلحات موضوعية: | Central Nervous System, Male, 0301 basic medicine, Encephalomyelitis, Autoimmune, Experimental, medicine.drug_class, Science, Sexism, Fluorescent Antibody Technique, General Physics and Astronomy, Thymus Gland, urologic and male genital diseases, Article, General Biochemistry, Genetics and Molecular Biology, Autoimmune Diseases, Myelin oligodendrocyte glycoprotein, 03 medical and health sciences, medicine, Animals, Humans, RNA, Messenger, Antigens, Promoter Regions, Genetic, 10. No inequality, Transcription factor, Autoimmune disease, Autoimmune encephalitis, Multidisciplinary, biology, Dihydrotestosterone, General Chemistry, medicine.disease, Autoimmune regulator, Androgen, Up-Regulation, Mice, Inbred C57BL, Androgen receptor, 030104 developmental biology, Receptors, Androgen, Immunology, Androgens, biology.protein, Female, Myelin-Oligodendrocyte Glycoprotein, Transcription Factors, medicine.drug |
| الوصف: | Male gender is protective against multiple sclerosis and other T-cell-mediated autoimmune diseases. This protection may be due, in part, to higher androgen levels in males. Androgen binds to the androgen receptor (AR) to regulate gene expression, but how androgen protects against autoimmunity is not well understood. Autoimmune regulator (Aire) prevents autoimmunity by promoting self-antigen expression in medullary thymic epithelial cells, such that developing T cells that recognize these self-antigens within the thymus undergo clonal deletion. Here we show that androgen upregulates Aire-mediated thymic tolerance to protect against autoimmunity. Androgen recruits AR to Aire promoter regions, with consequent enhancement of Aire transcription. In mice and humans, thymic Aire expression is higher in males compared with females. Androgen administration and male gender protect against autoimmunity in a multiple sclerosis mouse model in an Aire-dependent manner. Thus, androgen control of an intrathymic Aire-mediated tolerance mechanism contributes to gender differences in autoimmunity. Males are less susceptible to autoimmune diseases due to immunomodulatory effects of androgen. Here the authors show that androgen receptor upregulates Aire and Aire-dependent transcription in the thymic epithelium, and that Aire is required for androgen-mediated suppression of experimental autoimmune encephalitis. |
| اللغة: | English |
| تدمد: | 2041-1723 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::54395763e2de1befccb8af131c0ceca8 https://doaj.org/article/1221cac6180d456f84a5102f730cd069 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....54395763e2de1befccb8af131c0ceca8 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20411723 |
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