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Journal Article Epublish 11 citations

PubMed: 36428461 DOI: 10.3390/biomedicines10112893

Interleukin-33 Derived from Endometriotic Lesions Promotes Fibrogenesis through Inducing the Production of Profibrotic Cytokines by Regulatory T Cells.

Biomedicines 10(11)

Authors: Fengyi Xiao, Xishi Liu, Sun-Wei Guo

Affiliations

  • Gynecology Department, Shanghai Obstetrics and Gynecology Hospital, Fudan University, Shanghai 200011, China.
  • Gynecology Department, Shanghai Obstetrics and Gynecology Hospital, Fudan University, Shanghai 200011, China. Shanghai Key Laboratory of Female Reproductive Endocrine-Related Diseases, Fudan University, Shanghai 200011, China.

Abstract

In endometriosis, it has been widely believed that the local immunological milieu is Th2-skewed. Regulatory T cells (Tregs) promote fibrogenesis of endometriosis through the transforming growth factor β1 (TGF-β1) and platelet-derived growth factor (PDGF) signaling pathways. We aimed to explore whether Tregs in endometriotic lesions acquire increased production of effector cytokines under the influence of lesion-derived interleukin (IL)-33. We extracted lymphocytes from normal endometrium and ovarian endometrioma to evaluate the expression of IL-4, IL-13, interferon-γ (IFN-γ), TGF-β1, and the IL-33 receptor (ST2) by Tregs from these tissues. Colocalization of IL-33 and FOXP3 in normal endometrium and ovarian endometrioma was evaluated by immunofluorescence. Tregs and endometriotic stromal cells were co-cultured and treated with anti-IL-33 antibody, and the cytokines produced by Tregs were analyzed by flow cytometry and enzyme-linked immunosorbent assay (ELISA). Tregs in ovarian endometrioma produced significant amounts of IL-4, IL-13, TGF-β1, and ST2. Colocalization of IL-33 and FOXP3 was detected in ovarian endometrioma. IL-33 from endometriotic stromal cells caused the differentiation of lesional Tregs into type 2 T helper (Th2)-like cells, along with increased production of TGF-β1 by Tregs. Thus, Tregs and endometriotic lesions engage active crosstalk through IL-33 to promote fibrogenesis in endometriosis, and, as such, this finding opens up new avenues to identify novel therapeutic targets for endometriosis.

MeSH

Cytokines, Wounds And Injuries, Endometriosis, Platelet-Derived Growth Factor, Enzyme-Linked Immunosorbent Assay, Endometrium, Stromal Cells, Interleukin-13, T-Lymphocytes, Regulatory, Interleukin-33

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