Glucocorticoid receptor in T cells mediates protection from autoimmunity in pregnancy
Glucocorticoid receptor in T cells mediates protection from autoimmunity in pregnancy
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DOI：
10.1073/pnas.1617115114
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发表时间：
2017-01-10
影响因子：
11.1
通讯作者：
Friese, Manuel A.
中科院分区：
文献类型：
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作者：
Engler, Jan Broder;Kursawe, Nina;Friese, Manuel A.
妊娠是免疫耐受的最强诱因之一。包括多发性硬化症（MS）在内的许多自身免疫性疾病的疾病活动性会因怀孕而暂时受到抑制，但对其潜在的分子机制知之甚少。在这里，我们研究了常规T细胞和调节性T细胞（Tregs）在生殖过程中的内分泌调节。在体外，我们发现孕激素黄体酮通过与T细胞中的糖皮质激素受体（GR）混杂结合而显著增加Treg频率。在体内，发生实验性自身免疫性脑脊髓炎（EAE） （MS动物模型）的怀孕动物的t细胞特异性GR缺失导致Treg增加减少和妊娠诱导保护的选择性丧失，而生殖成功不受影响。我们的数据表明，类固醇激素可以通过对T细胞中GR的不同参与，使免疫平衡向有利于Tregs的方向转变。这种新定义的机制可以保护怀孕期间的自身免疫，并代表了未来治疗的潜在目标。
Pregnancy is one of the strongest inducers of immunological tolerance. Disease activity of many autoimmune diseases including multiple sclerosis (MS) is temporarily suppressed by pregnancy, but little is known about the underlying molecular mechanisms. Here, we investigated the endocrine regulation of conventional and regulatory T cells (Tregs) during reproduction. In vitro, we found the pregnancy hormone progesterone to robustly increase Treg frequencies via promiscuous binding to the glucocorticoid receptor (GR) in T cells. In vivo, T-cell-specific GR deletion in pregnant animals undergoing experimental autoimmune encephalomyelitis (EAE), the animal model of MS, resulted in a reduced Treg increase and a selective loss of pregnancy-induced protection, whereas reproductive success was unaffected. Our data imply that steroid hormones can shift the immunological balance in favor of Tregs via differential engagement of the GR in T cells. This newly defined mechanism confers protection from autoimmunity during pregnancy and represents a potential target for future therapy.