Mesenchymal stem cells enhance Treg immunosuppressive function at the fetal-maternal interface

• Published in: Journal of reproductive immunology Vol. 148; p. 103366
• Main Authors: Zhang, Di, Lin, Yikong, Li, Yunyun, Zhao, Dong, Du, Meirong
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier B.V 01.11.2021
• Subjects: Animals; CD4+T cell; Cells, Cultured; Disease Models, Animal; Female; Fetal-maternal immune tolerance; Forkhead Transcription Factors - metabolism; Humans; Immune Tolerance; Mesenchymal Stem Cells - physiology; Mice; MSCs; Placental Circulation; Pregnancy; T-Lymphocytes, Regulatory - immunology; Treg; Umbilical Cord - cytology; Pregnancy; CD4+T cell; MSCs; Treg; Fetal-maternal immune tolerance; CD4(+)T cell
• ISSN: 0165-0378; 1872-7603
• DOI: 10.1016/j.jri.2021.103366

•MSCs could induce expansion of decidual FOXP3+CD4+ T cells with upregulated production of IL-10 and TGF-β.•MSCs reinforced the immune suppressive functions of decidual Tregs (dTregs).•MSCs-instructed dTregs gained enhanced capacity to facilitate Th2 skewing while suppress Th1 and Th17 responses.•Adoptive transfer of MSCs effectively ameliorated LPS-induced embryo absorption rate with accumulated dTregs in uterine.•This study may offer a new insight for the application of MSCs and Tregs in clinical recurrent miscarriage. Well-regulated maternal-fetal immune tolerance is a prerequisite for normal pregnancy. Hyperactivated immune cells and overwhelming inflammatory responses trigger adverse gestation outcome, such as recurrent spontaneous abortion (RSA). Local exacerbation of immunomodulatory cells in maternal decidua is a critical event, tightly linked with fetus acceptance. Owning to the notable immunoregulatory potentials, mesenchymal stromal cells (MSCs) and regulatory T cells (Tregs) have been separately reported as promising therapeutic approaches for refractory RSA attributable to certain immune disorders. However, the cross-talk between MSCs and Tregs at the fetal-maternal interface remains poorly understood. Here we revealed, for the first time, that umbilical MSCs could induce expansion of decidual Foxp3+CD4+ T cells with upregulated production of IL-10 and TGF-β. Meanwhile, MSCs reinforced the immune suppressive functions of decidual Tregs (dTregs). More important, MSCs-instructed dTregs gained enhanced capacity to suppress Th1 and Th17 related inflammatory responses. In vivo data demonstrated that adoptive transfer of MSCs obviously promoted accumulation of Foxp3+ dTregs in lipopolysaccharide (LPS)-induced mice abortion model and spontaneous abortion model (DBA/2-mated female CBA/J mice). Furthermore, MSCs treatment effectively ameliorated absorption rate in both models. This study may offer a new insight for the application of MSCs and Tregs in clinical recurrent miscarriage.