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首页> 外文期刊>Hepatology: Official Journal of the American Association for the Study of Liver Diseases >Forkhead box p3+ regulatory T cell underlies male resistance to experimental type 2 autoimmune hepatitis.
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Forkhead box p3+ regulatory T cell underlies male resistance to experimental type 2 autoimmune hepatitis.

机译：前叉箱p3 +调节性T细胞是男性对实验性2型自身免疫性肝炎的抵抗力的基础。

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摘要

Autoimmune hepatitis (AIH), like many autoimmune diseases, is most prevalent in young women. The immunological basis of this age and sex susceptibility bias was investigated in a murine model of AIH. Xenoimmunization of 7-week-old female C57BL/6 mice resulted in more severe AIH with higher levels of liver inflammation, serum alanine aminotransferase, specific T-cell cytotoxicity, and autoantibody than younger and older females. Vaccinated males developed minimal liver inflammation and higher percentages of CD4(+)CD25(+)FoxP3(+) regulatory T cell in peripheral blood mononuclear cells, spleen, and liver than females. Regulatory T cells (Tregs) were virtually absent in liver-lymphocytes infiltrates of females. Castration of C57BL/6 mice, with or without 17beta-estradiol supplementation, did not modify susceptibility in males, nor Treg numbers, suggesting minimal contribution of testosterone and estradiol to autoimmune hepatitis (AIH) susceptibility. Xenoimmunized Aire(+/0) mouse displayed similar AIH susceptibility, sex bias, and Tregs numbers as C57BL/6 mice, suggesting that susceptibility in females is not the result of less stringent thymic central tolerance. Autoreactive B cell response against formiminotransferase-cyclodeaminase correlated with disease activity, possibly linking B-cell autoreactivity and AIH pathogenesis. CONCLUSION: Peripheral tolerance and development of regulatory T cells after self-mimicking antigen exposure, and not sexual hormone nor central tolerance, are the main factors for susceptibility to AIH in females.
机译：像许多自身免疫性疾病一样，自身免疫性肝炎（AIH）在年轻女性中最为普遍。在AIH小鼠模型中研究了该年龄和性别易感性偏倚的免疫学基础。 7周龄雌性C57BL / 6小鼠的异种免疫导致较年轻和较年长的雌性小鼠更严重的AIH，具有更高水平的肝脏炎症，血清丙氨酸转氨酶，特异性T细胞细胞毒性和自身抗体。接种疫苗的男性与女性相比，外周血单个核细胞，脾脏和肝脏中的肝脏炎症最小，CD4（+）CD25（+）FoxP3（+）调节性T细胞百分比更高。雌性的肝淋巴细胞浸润几乎不存在调节性T细胞（Tregs）。 C57BL / 6小鼠去势，无论是否添加17β-雌二醇，都不会改变雄性的易感性，也不会改变Treg的数量，这表明睾丸激素和雌二醇对自身免疫性肝炎（AIH）易感性的贡献很小。异种免疫的Aire（+ / 0）小鼠显示出与C57BL / 6小鼠相似的AIH易感性，性别偏倚和Tregs数，这表明雌性中的易感性不是胸腺中央耐受性较宽松的结果。对甲酰胺转移酶-环脱氨酶的自身反应性B细胞反应与疾病活动相关，可能与B细胞自身反应性和AIH发病机理有关。结论：自我模仿抗原暴露后的外周耐受性和调节性T细胞的发育，而不是性激素或中枢耐受性，是女性对AIH易感性的主要因素。

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