Progesterone Promotes Differentiation of Human Cord Blood Fetal T Cells into T Regulatory Cells but Suppresses Their Differentiation into Th17 Cells

  title={Progesterone Promotes Differentiation of Human Cord Blood Fetal T Cells into T Regulatory Cells but Suppresses Their Differentiation into Th17 Cells},
  author={Jeeho Lee and Benjamin J. Ulrich and Jung Yoon Cho and Jeongho Park and Chang H. Kim},
  journal={The Journal of Immunology},
  pages={1778 - 1787}
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… 

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Immunity and the Endocrine System


Impaired allogeneic activation and T-helper 1 differentiation of human cord blood naive CD4 T cells.
  • Li Chen, A. Cohen, D. Lewis
  • Biology, Medicine
    Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation
  • 2006
Cord blood CD4(+)CD25(+)-derived T regulatory cell lines express FoxP3 protein and manifest potent suppressor function.
It is found that cord blood was a superior source for Treg-cell isolation and cell line generation compared with adult blood, and banked cord blood specimens may serve as a readily available source of Treg cells for immunotherapy.
Conversion of Peripheral CD4+CD25− Naive T Cells to CD4+CD25+ Regulatory T Cells by TGF-β Induction of Transcription Factor Foxp3
Novel evidence is presented that conversion of naive peripheral CD4+CD25− T cells into anergic/suppressor cells that are CD25+, CD45RB−/low and intracellular CTLA-4+ can be achieved through costimulation with T cell receptors (TCRs) and transforming growth factor β (TGF-β).
The phenotype of human Th17 cells and their precursors, the cytokines that mediate their differentiation and the role of Th17 cells in inflammation.
While murine T(h)17 are pathogenic in some murine models of autoimmunity where T (h)1 cells seem to play a protective role, both T( h)17 and T(H)1 certainly contribute to the pathogenesis of human autoimmune and other chronic inflammatory disorders.
Induction of FOXP3 expression in naive human CD4+FOXP3 T cells by T-cell receptor stimulation is transforming growth factor-beta dependent but does not confer a regulatory phenotype.
It is demonstrated here that TCR stimulation alone was insufficient to induce Foxp3 expression in the absence of TGFbeta, whereas high levels of FOXP3 expression could be induced in the presence of T GFbeta, and this results suggest that even high Levels of FoxP3expression are insufficient to define a human CD4+ T cell as a T-regulatory cell.
Decidual and peripheral blood CD4+CD25+ regulatory T cells in early pregnancy subjects and spontaneous abortion cases.
It is shown that early human pregnancy decidua contains an abundance of CD4(+)CD25(bright) T cells, which express CD152(CTLA-4) at a high level, and these cells mediate potent inhibition of autologous T-cell proliferation by anti-CD3 stimulation and contribute to the mechanisms mediating maternal immune tolerance of conceptus antigens.
Systemic Reduction of Functionally Suppressive CD4dimCD25highFoxp3+ Tregs in Human Second Trimester Pregnancy Is Induced by Progesterone and 17β-Estradiol1
The view of hormones, particularly progesterone, as critical regulators of Tregs in pregnancy is supported, and early data on circulating Treg frequencies in pregnancy need reevaluation.
Progesterone increases systemic and local uterine proportions of CD4+CD25+ Treg cells during midterm pregnancy in mice.
It is demonstrated that P4 is an important regulator of systemic and local CD4(+)CD25(+) Treg cells, which are involved in maintaining maternal-fetal immune tolerance during midterm pregnancy.
Cutting Edge: Estrogen Drives Expansion of the CD4+CD25+ Regulatory T Cell Compartment1
The data suggest E2 promotes tolerance by expanding the regulatory T cell compartment by augmenting FoxP3 expression in vitro and in vivo, suggesting that high estrogen levels during pregnancy may help to maintain fetal tolerance.
Regulation of Trafficking Receptor Expression in Human Forkhead Box P3+ Regulatory T Cells1
It is found that human FOXP3+ T cells undergo changes in trafficking receptors according to their stages of activation and differentiation, which is potentially important for their tissue-specific migration and regulation of immune responses in humans.