MneSCs exert a supportive role in establishing a pregnancy-friendly microenvironment by inhibiting TH17 polarization. (April 2021)

• Record Type: Journal Article
• Authors: Ghanavatinejad, Alireza; Bozorgmehr, Mahmood; Shokri, Mohammad-Reza; Aleahmad, Mehdi; Tavakoli, Maryam; Shokri, Fazel; Zarnani, Amir-Hassan
• Is Part Of: Journal of reproductive immunology. Volume 144(2021)
• Publication Date: 2021-04
• Subjects: MenSCs -- TH17 -- Polarization -- Treg -- Proliferation -- Pregnancy; Reproduction -- Immunological aspects -- Periodicals; Immunology -- Periodicals; Allergy and Immunology -- Periodicals; Reproduction -- Periodicals; Reproduction -- Immunologie -- Périodiques; Immunologie -- Périodiques; Immunology; Reproduction -- Immunological aspects; Periodicals; Electronic journals; Electronic journals; 615.766
• DOI: 10.1016/j.jri.2020.103252
• Languages: English
• ISSNs: 0165-0378

Abstract

Highlights: MenSCs downregulate RORC and inhibit T CD4 + TH17 polarization. MenSCs managed to generate Tregs in a TH17 favored condition. Inhibition of PGE2 synergize with the capacity of MenSCs to hinder TH17 differentiation. MenSCs produce a considerable amount of IDO and increased Treg/Th17 ratio. Abstract: Objectives: Uncontrolled TH17 differentiation has been suggested to play a role in the pathogenesis of pregnancy loss. We recently showed that menstrual blood stromal/stem cells (MenSCs) alter functional features of natural killer cells. Here, we hypothesized that MenSCs could modulate differentiation of TH17 cells. Method: MenSCs were collected from 18 apparently healthy women and characterized. Bone marrow mesenchymal stem cells (BMSCs) served as a control. TH17 polarization and proliferation of purified T CD4+ cells were assessed by flow cytometry in a well-defined co-culture system containing T CD4+ cells and MenSCs or BMSCs. Indoleamine 2, 3-Dioxygenase (IDO) activity was evaluated in MenSC and BMSC culture supernatants by a colorimetric assay. The impact of MenSCs on expression of transcription factors, RORC, T-bet, Gata3, NRP-1 and Helios were studied by qPCR. Results: MenSCs significantly inhibited TH17 differentiation (p = 0.0383) and percentage of the cells co-expressing IL-17 and IFN-γ (p = 0.0023). PGE2 blockade significantly reduced percentage and proliferation of T CD4+IL-17+ (p = 0.003, p = 0.0018), T CD4+ IFN-γ+ (p = 0.002, p = 0.0022) and T CD4+IL-17+ IFN-γ+ (p = 0.004, p = 0.02) cells. MenSCs produced a considerable activity of IDO (p = 0.0002), induced a significant rise in the Treg frequency (p = 0.0091) and a sharp increase in TH17/Tregs ratio (p = 0.0022). MenSCs increased expression of NRP1 (p = 0.001), while downregulated expression of RORC in T cells (p = 0.001). Conclusion: Our results suggest a supportive role for MenSCs in establishing a pregnancy-friendly microenvironment in the uterus and put forth the idea that inherent abnormalities of MenSCs may be a basis for dysregulated endometrial immune network leading to pregnancy loss.