Progesterone promotes differentiation of human cord blood fetal T cells into T regulatory cells but suppresses their differentiation into Th17 cells.
Progesterone promotes differentiation of human cord blood fetal T cells into T regulatory cells but suppresses their differentiation into Th17 cells.
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DOI：
10.4049/jimmunol.1003919
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发表时间：
2011-08-15
期刊：
影响因子：
--
通讯作者：
Kim CH
中科院分区：
文献类型：
--
作者：
Lee JH;Ulrich B;Cho J;Park J;Kim CH
孕激素是维持妊娠的一种重要的女性性激素，对免疫反应的调节有着深远的影响。我们在这里报告了一种新的功能，孕激素在调节幼稚脐带血（CB）胎儿T细胞分化为关键的调节性T细胞亚群。预后驱动同种异体活化诱导的CB幼稚T细胞（而非成人外周血（PB）T细胞）分化为免疫抑制性T调节细胞（TCR 4），其中许多表达FoxP 3。与在没有孕酮的情况下诱导的那些相比，在孕酮的存在下诱导的FoxP 3 + T细胞高度表达记忆T细胞标志物。在这方面，富含孕酮的CB中的Treg区室富含记忆型FoxP 3 + T细胞。此外，CB抗原呈递细胞在诱导FoxP 3 + T细胞方面比它们的PB对应物更有效。我们发现孕酮的另一个相关功能是抑制CB CD 4 + T细胞分化为炎症相关的Th 17细胞。孕酮响应于IL-2而增强STAT 5的活化，而其响应于IL-6而降低STAT 3的活化，这与孕酮在产生Tcl 4细胞相对于Th 17细胞中的选择性活性一致。此外，孕酮对T细胞表达IL-6受体具有抑制功能。结果确定了孕激素在调节胎儿T细胞分化以促进免疫耐受中的新作用。
Progesterone, a key female sex hormone with pleiotropic functions in maintenance of pregnancy, has profound effects on regulation of immune responses. We report here a novel function of progesterone in regulation of naïve cord blood (CB) fetal T cell differentiation into key regulatory T cell subsets. Progesterone drives allogeneic activation-induced differentiation of CB naive, but not adult peripheral blood (PB), T cells into immune suppressive T regulatory cells (Tregs), many of which express FoxP3. Compared to those induced in the absence of progesterone, the FoxP3+ T cells induced in the presence of progesterone highly expressed memory T cell markers. In this regard, the Treg compartment in progesterone-rich CB is enriched with memory type FoxP3+ T cells. Moreover, CB antigen presenting cells were more efficient in inducing FoxP3+ T cells than their PB counterparts. Another related function of progesterone that we discovered was to suppress the differentiation of CB CD4+ T cells into inflammation-associated Th17 cells. Progesterone enhanced activation of STAT5 in response to IL-2 while it decreased STAT3 activation in response to IL-6, which is in line with the selective activity of progesterone in generation of Tregs versus Th17 cells. Additionally, progesterone has a suppressive function on the expression of the IL-6 receptor by T cells. The results identified a novel role of progesterone in regulation of fetal T cell differentiation for promotion of immune tolerance.
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影响因子：
29.4
作者：
Kang SG;Wang C;Matsumoto S;Kim CH
通讯作者：
Kim CH
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作者：
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