title: Progesterone promotes differentiation of human cord blood fetal T cells into T regulatory cells but suppresses their differentiation into Th17 cells.
abstract: Progesterone, a key female sex hormone with pleiotropic functions in maintenance of pregnancy, has profound effects on regulation of immune responses. We report in this work a novel function of progesterone in regulation of naive cord blood (CB) fetal T cell differentiation into key T regulatory cell (Treg) subsets. Progesterone drives allogeneic activation-induced differentiation of CB naive, but not adult peripheral blood, T cells into immune-suppressive Tregs, many of which express FoxP3. Compared with 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 APCs were more efficient than their peripheral blood counterparts in inducing FoxP3(+) T cells. 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, whereas 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.
authors.affiliation: Laboratory of Immunology and Hematopoiesis, Department of Comparative Pathobiology, Center for Cancer Research, Purdue University, West Lafayette, IN 47907, USA.
authors.forename: Jee H
authors.initials: JH
authors.lastname: Lee
authors.forename: Benjamin
authors.initials: B
authors.lastname: Ulrich
authors.forename: Jungyoon
authors.initials: J
authors.lastname: Cho
authors.forename: Jeongho
authors.initials: J
authors.lastname: Park
authors.forename: Chang H
authors.initials: CH
authors.lastname: Kim
mesh_terms: D000328:Adult; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology*; D005260:Female; D005312:Fetal Blood / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D051858:Forkhead Transcription Factors / Q000276:immunology / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology; D006801:Humans; D007108:Immune Tolerance / Q000187:drug effects / Q000502:physiology*; D007376:Interleukin-2 / Q000276:immunology / Q000378:metabolism; D015850:Interleukin-6 / Q000276:immunology / Q000378:metabolism; D011247:Pregnancy; D011374:Progesterone / Q000276:immunology* / Q000494:pharmacology; D011372:Progestins / Q000276:immunology / Q000494:pharmacology; D019947:Receptors, Interleukin-6 / Q000276:immunology / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000276:immunology / Q000378:metabolism; D050799:STAT5 Transcription Factor / Q000276:immunology / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D058504:Th17 Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism
chemical_list: C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; C508594:IL2 protein, human; C508600:IL6 protein, human; D007376:Interleukin-2; D015850:Interleukin-6; D011372:Progestins; D019947:Receptors, Interleukin-6; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D050799:STAT5 Transcription Factor; D011374:Progesterone