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Inflammatory bowel disease (IBD) is a chronic condition characterized by gastrointestinal tract inflammation and still lacks satisfactory treatments. Mesenchymal stromal cells (MSCs) show promising potential for treating IBD, but their therapeutic efficacy varies depending on the tissue of origin. We aim to investigate whether intestine Peyer's patch (PP)‐derived MSCs have superior immunomodulatory effects on T cells and better therapeutic effects on IBD compared with bone marrow‐derived MSCs. We isolated PPs‐derived Nestin+ MSCs (MSCsPP) and bone marrow‐derived Nestin+ MSCs (MSCsBM) from Nestin‐GFP transgenic mice to explore their curative effects on murine IBD model. Moreover, we tested the effects of IL‐22 knockdown and IL‐22 overexpression on the therapeutic efficacy of MSCsPP and MSCsBM in murine IBD, respectively. We demonstrated that Nestin+ cells derived from murine PPs exhibit MSC‐like biological characteristics. Compared with MSCsBM, MSCsPP possess enhanced immunoregulatory ability to suppress T cell proliferation and inflammatory cytokine production. Moreover, we observed that MSCsPP exhibited greater therapeutic efficacy than MSCsBM in murine IBD models. Interestingly, IL‐22, which was highly expressed in MSCsPP, could alleviate the severity of the intestinal inflammation, while knockdown IL‐22 of MSCsPP remarkably weakened the therapeutic effects. More importantly, IL‐22 overexpressing MSCsBM could significantly improve the symptoms of murine IBD models. This study systemically demonstrated that murine MSCsPP have a prominent advantage in murine IBD treatment, partly through IL‐22. [ABSTRACT FROM AUTHOR]

Cell-cell contact participates in the process of mesenchymal stromal cell (MSC)-mediated T cell modulation and thus contributes to MSC-based therapies for various inflammatory diseases, especially T cell-mediated diseases. However, the mechanisms underlying the adhesion interactions between MSCs and T cells are still poorly understood. In this study, we explored the interaction between MSCs and T cells and found that activated T cells could rapidly adhere to MSCs, leading to significant reduction of TNF-α and IFN-γ mRNA expression. Furthermore, TCR-proximal signaling in activated T cells was also dramatically suppressed in the MSC co-culture, resulting in weakened Ca2+ signaling. MSCs rapidly suppressed TCR signaling and its downstream signaling in a cell-cell contact-dependent manner, partially through the ICAM-1/CD43 adhesion interaction. Blockade of either ICAM-1 on MSCs or CD43 on T cells significantly reversed this rapid suppression of proinflammatory cytokine expression in T cells. Mechanistically, MSC-derived ICAM-1 likely disrupts CD43-mediated TCR microcluster formation to limit T cell activation. Taken together, our results reveal a fast mechanism of activated T cell inhibition by MSCs, which provides new clues to unravel the MSC-mediated immunoregulatory mechanism for aGVHD and other severe acute T cell-related diseases. [ABSTRACT FROM AUTHOR]

Myeloid-derived suppressor cells (MDSCs) are a population of immature myeloid cells defined by their immunosuppression. Elevated levels of certain soluble cytokines in tumor microenvironment, such as IL-6 and IL-10, contribute to the recruitment and accumulation of tumor-associated MDSCs. In turn, MDSCs secret IL-6 and IL-10 and form a positive self-feedback to promote self-expansion. MDSCs also release other soluble cytokines such as TGF-β and chemokines to exert their suppressive function by induction of regulatory T cells. Exhaustion of some amino acids by MDSCs with many secretory enzymes or membrane transporters as well as their metabolites leads to blockage of T cells development. The interaction of membrane molecules on MDSCs and T cells leads inactivation and apoptosis of T cells. There may be one or some dominant mechanism(s) by which MDSCs impair the immune system in different tumor microenvironment. Thus, it is important to identify the subpopulations of MDSCs and clarify the dominant mechanism(s) through which MDSCs inhibit antitumor immunity in order to establish a more individual immunotherapy by eliminating MDSCs-mediated suppression. Currently studies concentrated on therapeutic strategies targeting MDSCs have obtained promising results. However, more studies are needed to demonstrate their clinical safety and efficacy. [ABSTRACT FROM AUTHOR]