Interleukin 17 (IL-17)-Induced Mesenchymal Stem Cells Prolong the Survival of Allogeneic Skin Grafts

Abstract

BackgroundMesenchymal stem cells (MSCs) have the potential of self-renewal and multi-differentiation and have a wide application prospect in organ transplantation for the effect of inducing immune tolerance. It has found that interleukin 17 (IL-17) could enhance the inhibition effect of MSCs on T cell proliferation and increase the immunosuppressive effect of MSCs. In this study, we aimed to investigate the effect of IL-17-induced MSCs on allograft survival time after transplantation.Material/MethodsBMSCs were characterized by differential staining. The allogenic skin transplantations were performed and the BMSCs pre-treated by IL-17 were injected. To assess the immunosuppressive function of IL-17-induced BMSCs, the morphology of the grafts, the homing ability of the BMSCs, and the survival time of the grafts were analyzed.ResultsBMSCs from BALB/c have multidirectional differentiation potential to differentiate into osteogenic, chondrogenic, and adipogenic lineage cells. IL-17-induced BMSCs prolonged the survival time of allogeneic skin grafts dramatically. We found that there were more labeled MSCs in the skin grafts, and the Treg subpopulations percentage, IL-10, and TGF-β were significantly increased, while the IFN-γ level was decreased compared to the control group and MSCs group. In conclusion, IL-17 can enhance the homing ability of MSCs and regulate the immunosuppressive function of MSC.ConclusionsOur data demonstrate that IL-17 plays the crucial role in MSC homing behaviors and promotes immunosuppression of MSCs during transplantation procedures, suggesting that IL-17-pre-treated MSCs have potential to prolong graft survival and reduce transplant rejection.

Bone Regeneration, Reconstruction and Use of Osteogenic Cells; from Basic Knowledge, Animal Models to Clinical Trials

“…The immunosuppression of effector functions, preventing the development of immunological diseases, is possible due to the communication of innate and adaptive immune cells with MSCs via inflammatory cytokines e.g., IL17, IL-6, IFN-γ and growth factors e.g., hepatocyte growth factor (HGF), prostaglandin E2 (PGE2), transforming growth factor-β (TGF-β) [95]. Furthermore, the inhibitory effects of MSCs on the proliferation of T cells are dependent on the expression of interleukin 17 (IL- 17), such that in mice, IL-17-induced mesenchymal stem cells had their homing ability enhanced, resulting in the prolonged survival time of allogeneic skin grafts through suppressed immune recognition [96]. Interleukin IL-6 stimulates the proliferation and survival of T cells, in contrast to interferon-γ (IFN-γ), which suppress the proliferation of regulatory T cells and other immune cells [97].…”

Save your gut save your age: The role of the microbiome in stem cell ageing

“…In the bone, both IL-6, IL-10 and TNFα have shown a positively associated with the differentiation of bone marrow stem cells 65. In the skin grafts, IL-17 promotes the self-renewal and differentiation of mesenchymal stem cells 66. In line with this hypothesis, alterations in gut microbiota attenuate the systemic and hepatic inflammation in obese and diabetic mice by restoring endogenous intestinotrophic proglucagon-derived peptide-dependent modulations of the gut permeability 67.…”

TL1A/TNFR2 Axis Enhances Immunoregulatory Effects of Bone Marrow Derived Mesenchymal Stem Cell by Indian Hedgehog Signaling Pathway

“…Besides, IL-7 promoted renal regeneration by enhancing the fusion ability of rat BMSCs ( 41 ). Moreover, IL-17-stimulated MSCs increased survival of skin transplant from allogenic source ( 42 ), and IL-17a-pretreated MSCs characteristically increased the therapeutic efficiency in renal diseases ( 43 ), whereas IL-17b promoted the immunoregulatory potency of MSCs in the treatment of gastric diseases ( 44 ). IL-22 promoted MSCs migration, proliferation, and osteogenic differentiation ( 45 ).…”