Dept. of Medicine, University of Washington, Seattle, WA 98195, USA.
J Leukoc Biol. 2013 Mar;93(3):369-75. doi: 10.1189/jlb.1012491. Epub 2013 Jan 10.
Pg has distinct immunomodulatory properties involved in poorly understood immune phenomena, including maternal tolerance of the fetus, increased risk of certain infections during pregnancy or after Pg birth control, and pregnancy-associated remission of autoimmune disease. Several potential mechanisms have been identified, including alteration of Th1 and Treg activity, but the precise cellular and molecular targets of Pg immunomodulation in vivo remain obscure, partly because Pg can signal through several different receptor types. One such receptor, the iPR, encoded by the pgr gene, is essential for reproduction in female mice and is expressed in the thymus and CD4(+) T cells. We hypothesized that iPR regulates CD4(+) T cell activity and adaptive immune responses in vivo. With the use of iPR KO mice, we demonstrate that iPR specifically suppresses TD antibody responses, primarily by dampening CD4(+) Teff activity, likely via transcriptional repression of the IFN-γ gene and modulation of other programs regulating CD4(+) T cells. Our results highlight a novel mechanism linking the endocrine and immune systems, and they offer insight into important but poorly understood phenomena in women's health and autoimmunity.
PG 具有独特的免疫调节特性，涉及到一些尚未被充分理解的免疫现象，包括母体对胎儿的耐受性、妊娠期间或 PG 避孕后某些感染的风险增加，以及与妊娠相关的自身免疫病缓解。已经确定了几种潜在的机制，包括 Th1 和 Treg 活性的改变，但 PG 在体内免疫调节的确切细胞和分子靶点仍然不清楚，部分原因是 PG 可以通过几种不同的受体类型发出信号。这样的一种受体是 iPR，由 pgr 基因编码，是雌性小鼠繁殖所必需的，并且在胸腺和 CD4(+)T 细胞中表达。我们假设 iPR 在体内调节 CD4(+)T 细胞的活性和适应性免疫反应。使用 iPR KO 小鼠，我们证明 iPR 特异性地抑制 TD 抗体反应，主要是通过抑制 CD4(+)Teff 活性来实现，可能是通过 IFN-γ 基因的转录抑制和调节其他调节 CD4(+)T 细胞的程序来实现。我们的结果强调了内分泌和免疫系统之间的一种新的联系机制，并为女性健康和自身免疫领域中一些重要但尚未被充分理解的现象提供了深入的了解。
