Gender bias in autoimmunity is influenced by microbiota.

Gender bias in autoimmunity is influenced by microbiota.
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DOI:
10.1016/j.immuni.2013.08.013
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发表时间:
2013-08-22
期刊:
影响因子:
32.4
通讯作者:
Chervonsky AV
Chervonsky AV
中科院分区:
医学1区
文献类型:
--
作者:
Yurkovetskiy L;Burrows M;Khan AA;Graham L;Volchkov P;Becker L;Antonopoulos D;Umesaki Y;Chervonsky AV

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性别偏见和性激素在自身免疫性疾病中的作用已经得到了很好的证实。在无特定病原体(SPF)非肥胖糖尿病(NOD)小鼠中,雌性1型糖尿病(T1 D)的发病率高1.3-4.4倍。无菌(GF)小鼠失去了性别偏见(雌性/雄性比1.1-1.2)。男性和女性的肠道微生物群不同,男性阉割的趋势逆转,证实雄激素影响肠道微生物群。具有确定的微生物群的GF NOD小鼠的定殖显示,在雄性小鼠中过度代表的一些但不是全部谱系支持T1 D的性别偏见。虽然,男性的保护与血液雄激素浓度无关,但选择的微生物谱系的扩张可能是一种正反馈机制,有助于自身免疫性疾病的性二型性。基因表达分析表明,微生物群参与保护男性免受T1 D的途径。我们的研究结果支持性别偏见的双信号模型,其中激素和微生物一起触发保护途径。
Gender bias and the role of sex hormones in autoimmune diseases are well established. In specific pathogen-free (SPF) non-obese diabetic (NOD) mice, females have 1.3–4.4 times higher incidence of Type 1 diabetes (T1D). Germ-free (GF) mice lost the gender bias (female/male ratio 1.1–1.2). Gut microbiota differed in males and females, a trend reversed by male castration confirming that androgens influence gut microbiota. Colonization of GF NOD mice with defined microbiota revealed that some, but not all, lineages overrepresented in male mice supported a gender bias in T1D. Although, protection of males did not correlate with blood androgen concentration, hormone-supported expansion of selected microbial lineages may work as a positive feedback mechanism contributing to the sexual dimorphism of autoimmune diseases. Gene expression analysis suggested pathways involved in protection of males from T1D by microbiota. Our results favor a two-signal model of gender bias, in which hormones and microbes together trigger protective pathways.
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