Olfactory Ecto-Mesenchymal Stem Cell-Derived Exosomes Ameliorate Experimental Colitis via Modulating Th1/Th17 and Treg Cell Responses

Abstract

Olfactory ecto-mesenchymal stem cells (OE-MSCs) are a novel population of resident stem cells in the olfactory lamina propria with strong immunosuppressive function. Exosomes released by MSCs are considered to carry various mRNAs, microRNAs and proteins from cells and function as an extension of MSCs. However, it remains unclear whether exosomes derived from OE-MSCs (OE-MSCs-Exos) possess any immunoregulatory functions. In this study, we found that OE-MSCs-Exos possessed strong suppressive function in CD4+T cell proliferation, accompanied by reduced IL-17, IFN-γ and enhanced TGF-β, IL-10 secreted by T cells. In experimental colitis mice, treatment of OE-MSCs-Exos markedly alleviated the severity of disease, and Th1/Th17 subpopulations were remarkably reduced whereas Treg cells were increased after OE-MSCs-Exos treatment. Mechanistically, OE-MSCs-Exos were demonstrated to inhibit the differentiation of Th1 and Th17 cells, but promote the induction of Treg cells in vitro. Taken together, our findings identified a novel function of OE-MSCs-Exos in regulating T-cell responses, indicating that OE-MSCs-Exos may represent a new cell-free therapy for the treatment of IBD and other inflammatory diseases.

Effects of Mesenchymal Stem Cell-Derived Exosomes on Autoimmune Diseases

“…Previous studies in our laboratory have also found that OE-MSC-EXOs had a potent inhibitory effect on the proliferation of CD4 + T cells in experimental colitis mice. At the same time, the secretion of IL-17 and IFN-γ by T cells was reduced, whereas the secretion of TGF-β and IL-10 was enhanced, which could significantly slow disease progression ( 77 ). Following treatment with OE-MSC-EXOs, the Th1/Th17 subsets were significantly reduced, while Treg cells were increased ( 77 ).…”

“…At the same time, the secretion of IL-17 and IFN-γ by T cells was reduced, whereas the secretion of TGF-β and IL-10 was enhanced, which could significantly slow disease progression ( 77 ). Following treatment with OE-MSC-EXOs, the Th1/Th17 subsets were significantly reduced, while Treg cells were increased ( 77 ). It was found that transgene-free human induced pluripotent stem cells (iPSCs) derived EVs could prevent the progression of Sjögren’s syndrome (SS) by inhibiting the differentiation of follicular helper T (Tfh) and Th17 cells ( 78 ).…”

“…Other tissue-derived MSC-EXOs showed similar efficacy to that of hUC-MSC-EXOs in the treatment of DSS induced IBD. OE-MSC-EXOs significantly improved the severity of experimental colitis in mice primarily by modulating the immune response of Th-cells, including a significant reduction in Th1/Th17 subsets and an increase in Treg cells ( 77 ). Neda Heidari et al.…”

Exosomes as a New Delivery Vehicle in Inflammatory Bowel Disease

“…Further, OE-MSC-Exo promote the induction of Tregs and inhibit the differentiation of Th1 and Th17 cells. The function of OE-MSC-Exo in regulating T cell responses suggests that the OE-MSC-Exo may be a new target for the treatment of IBD [64].…”

A novel therapeutic approach for inflammatory bowel disease by exosomes derived from human umbilical cord mesenchymal stem cells to repair intestinal barrier via TSG-6

“…The therapeutic effects of MSCs-Exo have been demonstrated in colitis mouse model [ 13 – 15 ]. In terms of mechanisms, studies recently reported that MSCs-Exo attenuate colitis through increasing the proportion of Treg cells and M2 macrophages [ 16 , 17 ]. However, the effect of MSCs-Exo on the intestinal mucosal barrier remains unclear.…”