Medroxyprogesterone Acetate Decreases Th1, Th17, and Increases Th22 Responses via AHR Signaling Which Could Affect Susceptibility to Infections and Inflammatory Disease

A synthetic progestin, medroxyprogesterone acetate (MPA), was used in a novel study to determine progestin effects on human purified macrophages and Th1, Th2, Th17, Th22 cells. MPA concentrations were equivalent to those in the serum of women after 6 and 9 months of progestin use. MPA has no effect...

Full description

Saved in:
Bibliographic Details
Published inFrontiers in immunology Vol. 10; p. 642
Main Authors Piccinni, Marie-Pierre, Lombardelli, Letizia, Logiodice, Federica, Kullolli, Ornela, Maggi, Enrico, Barkley, Marylynn S.
Format Journal Article
LanguageEnglish
Published Switzerland Frontiers Media S.A 03.04.2019
Subjects
contraception
hormone replacement therapy
Immunology
medroxyprogesterone acetate
Th1
Th17
Th2
infection
Th22
medroxyprogesterone acetate
hormone replacement therapy
Th1
Th17
contraception
Th2
Online AccessGet full text
ISSN1664-3224
1664-3224
DOI10.3389/fimmu.2019.00642

Cover

More Information
Summary:A synthetic progestin, medroxyprogesterone acetate (MPA), was used in a novel study to determine progestin effects on human purified macrophages and Th1, Th2, Th17, Th22 cells. MPA concentrations were equivalent to those in the serum of women after 6 and 9 months of progestin use. MPA has no effect on the proliferation of PBMCs and CD4+ T cell clones induced by immobilized anti-CD3 antibodies or by antigen (streptokinase). However, MPA decreases production and mRNA expression of IL-5, IL-13, IFN-γ, T-bet, RORC, and IL-17A but increases production and mRNA expression of IL-22 by CD4+ Th22 cell clones and decreases IL-22 production by Th17 cells. MPA inhibits RORC, but not T-bet and AHR, by Th17 cells but increases AHR mRNA and T-bet expression of established CD4+ Th22 cell clones. This suggests that MPA, at concentrations equivalent to those found in the serum of women after treatment for contraception and hormone replacement therapy, can directly inhibit Th1 responses (against intracellular bacteria and viruses), Th17 (against extracellular bacteria and fungi), Th2 (against parasites) but MPA therapy increases IL-22 produced by Th22 cells mediated by an increased expression of AHR and T-bet controlling inflammation. MPA could be responsible for the tissue damage limited by IL-22 in absence of IL-17A.
Bibliography:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
Edited by: Detlef Neumann, Hannover Medical School, Germany
This article was submitted to Cytokines and Soluble Mediators in Immunity, a section of the journal Frontiers in Immunology
Reviewed by: Ana Claudia Zenclussen, Universitätsklinikum Magdeburg, Germany; Cristiana Stellato, University of Salerno, Italy; Roberta Bulla, University of Trieste, Italy
ISSN:1664-3224
1664-3224
DOI:10.3389/fimmu.2019.00642