ESPEYB15 14 Science and Medicine Why do women have more autoimmune disease than men? (1 abstracts)
14.1 Estrogen receptor α contributes to T cell–mediated autoimmune inflammation by promoting T cell activation and proliferation
Mohammad I , Starskaia I , Nagy T , Guo J , Yatkin E , Väänänen K , Watford WT & Chen Z
To read the full abstract: Sci. Signal. 2018;11:eaap9415
Women are more frequently affected by autoimmune disorders than men. A role for estrogen was suggested by the observation that the development of inflammatory bowel disease was associated with oral contraceptive use. Women also respond to infection and vaccination with higher antibody production and a T helper 2 (TH2) cell–dominant immune responses, whereas men usually show TH1 cell–biased immune responses.
Here, Mohammad et al. identify a direct role for estrogen in the development of autoimmune T cell responses through its estrogen receptor α (ERα) in a mouse model of colitis. ERα-expressing T cells were more activated after stimulation, proliferated more, and expressed more proinflammatory cytokines than T cells lacking this receptor. Other scientists have shown that the X-chromosome also matters; individuals with Klinefelter syndrome (47,XXY) have increased incidence of systemic lupus (SLE). This suggests that X chromosome dosage could be an important risk factor in SLE. Souyris et al. (1) recently demonstrated that Toll-like receptor 7 (TLR7), which is encoded on the X chromosome, escapes X inactivation in B cells and myeloid cells in females and Klinefelter individuals. TLR7 binds single-stranded RNA and activates type I interferon signaling, a pathway that is also activated in SLE patients. Thus, biallelic expression of TLR7 appears to contribute to greater SLE risk.
1. Souyris M, Cenac C, Azar P, Daviaud D, Canivet A, Grunenwald S, Pienkowski C, Chaumeil J, Mejia JE, Guery JC. TLR7 escapes X chromosome inactivation in immune cells. Sci Immunol 2018; Jan 26;3(19). pii: eaap8855.
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ESPE Yearbook of Paediatric Endocrinology
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