The risk of developing systemic lupus erythematosus (SLE) is about 9 times higher in women as compared to men. Our recent report, which used (SWRxNZB) F1 (SNF1) mouse model of spontaneous lupus, showed a potential link between immune response initiated in the gut mucosa at juvenile age (sex hormone independent) and SLE susceptibility. Here, using this mouse model, we show that gut microbiota contributes differently to pro-inflammatory immune response in the intestine and autoimmune progression in lupus-prone males and females. We found that gut microbiota composition in male and female littermates are significantly different only at adult ages. However, depletion of gut microbes causes suppression of autoimmune progression only in females. In agreement, microbiota depletion suppressed the pro-inflammatory cytokine response of gut mucosa in juvenile and adult females. Nevertheless, microbiota from females and males showed, upon cross-transfer, contrasting abilities to modulate disease progression. Furthermore, orchidectomy (castration) not only caused changes in the composition of gut microbiota, but also a modest acceleration of autoimmune progression. Overall, our work shows that microbiota-dependent pro-inflammatory immune response in the gut mucosa of females initiated at juvenile ages and androgen-dependent protection of males contribute to gender differences in the intestinal immune phenotype and systemic autoimmune progression.

中文翻译：

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肠道菌群对雌性和雄性狼疮易感小鼠的肠道免疫表型和全身自身免疫进程有不同的贡献。

女性患系统性红斑狼疮（SLE）的风险是男性的9倍。我们最近的报告使用了自发性狼疮的（SWRxNZB）F1（SNF1）小鼠模型，显示了幼年时肠粘膜发起的免疫反应（与性激素无关）与SLE易感性之间存在潜在的联系。在这里，使用这种小鼠模型，我们显示肠道微生物群在易患狼疮的雄性和雌性肠道中的促炎性免疫应答和自身免疫进程中有不同的贡献。我们发现，男性和女性同窝仔的肠道菌群组成只有在成年年龄时才显着不同。但是，肠道微生物的耗竭仅在女性中导致自身免疫进程的抑制。同意 微生物群消耗抑制了幼年和成年女性肠道黏膜的促炎性细胞因子反应。然而，来自雌性和雄性的微生物群在交叉转移后显示出调节疾病进展的相反能力。此外，兰花切除术（cast割）不仅引起肠道菌群组成的变化，而且还导致自身免疫进程的适度加速。总体而言，我们的工作表明，在幼年时开始的雌性肠道粘膜中的微生物群依赖性促炎免疫反应和雄性激素的依赖性保护作用导致肠道免疫表型和全身自身免疫进展的性别差异。睾丸切除术（ration割）不仅会导致肠道菌群组成的变化，还会导致自身免疫进程的适度加速。总体而言，我们的工作表明，在幼年时开始的雌性肠道粘膜中的微生物群依赖性促炎免疫反应和雄性激素的依赖性保护作用导致肠道免疫表型和全身自身免疫进展的性别差异。睾丸切除术（ration割）不仅会导致肠道菌群组成的变化，还会导致自身免疫进程的适度加速。总体而言，我们的工作表明，在幼年时开始的雌性肠道粘膜中的微生物群依赖性促炎免疫反应和雄性激素的依赖性保护作用导致肠道免疫表型和全身自身免疫进展的性别差异。