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Publication : The intracellular progesterone receptor regulates CD4+ T cells and T cell-dependent antibody responses.

First Author  Hughes GC Year  2013
Journal  J Leukoc Biol Volume  93
Issue  3 Pages  369-75
PubMed ID  23307939 Mgi Jnum  J:198073
Mgi Id  MGI:5495362 Doi  10.1189/jlb.1012491
Citation  Hughes GC, et al. (2013) The intracellular progesterone receptor regulates CD4+ T cells and T cell-dependent antibody responses. J Leukoc Biol 93(3):369-75
abstractText  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-gamma 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.
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