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-g, 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 thatMPA, 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.

Medroxyprogesterone acetate decreases Th1, Th17, and increases Th22 responses via AhR signaling which could affect susceptibility to infections and inflammatory disease / Piccinni M.P.; Lombardelli L.; Logiodice F.; Kullolli O.; Maggi E.; Barkley M.S.. - In: FRONTIERS IN IMMUNOLOGY. - ISSN 1664-3224. - ELETTRONICO. - 10:(2019), pp. 642-656. [10.3389/fimmu.2019.00642]

Medroxyprogesterone acetate decreases Th1, Th17, and increases Th22 responses via AhR signaling which could affect susceptibility to infections and inflammatory disease

Piccinni M. P.
;
Lombardelli L.;Logiodice F.;Kullolli O.;Maggi E.;
2019

Abstract

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-g, 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 thatMPA, 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.
2019
10
642
656
Goal 3: Good health and well-being for people
Piccinni M.P.; Lombardelli L.; Logiodice F.; Kullolli O.; Maggi E.; Barkley M.S.
File in questo prodotto:
File Dimensione Formato  
fimmu-10-00642.pdf

accesso aperto

Descrizione: MPA , un contracettivo, riducendo le risposte Th1 e Th17 e aumentando le risposte Th22 potrebbe avere un influenza sulla succetibilità delle pazienti a contrarre infezioni
Tipologia: Pdf editoriale (Version of record)
Licenza: Open Access
Dimensione 3.77 MB
Formato Adobe PDF
3.77 MB Adobe PDF

I documenti in FLORE sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificatore per citare o creare un link a questa risorsa: https://hdl.handle.net/2158/1162578
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 29
  • ???jsp.display-item.citation.isi??? 25
social impact