Abstract
Mesenchymal stem cells (MSCs) show significant therapeutic effects in type 1 diabetes mellitus (T1DM) as regulating the inflammatory processes. However, little is known about the detailed process of MSCs immunosuppression in T1DM. In this study, we investigated the effects of wild-type p53-induce phosphatase 1 (Wip1) on regulating MSCs immunosuppressive capacities in T1DM mice. We found that Wip1 knockout (Wip1−/−) MSCs had lower therapeutic effects in T1DM mice, and displayed weaker immunosuppressive capability. In vivo distribution analysis results indicated thatWip1−/−MSCs could home to the damaged pancreas and increase the expression of tumor necrosis factor-α (TNF-α), interleukin-17a (IL-17a), interferon-α(IFN-α), IFN-β, and IFN-γ, while decrease the expression of IL-4 and IL-10. Moreover, we confirmedWip1−/−MSCs exhibited weaker immunosuppressive capacity, as evidenced by enhanced expression of bone marrow stromal cell antigen 2(BST2) and IFN-α. In conclusion, these results revealed Wip1 affects MSCs immunomodulation by regulating the expression of IFN-α/BST2. Our study uncovered that Wip1 is required to regulate the therapeutic effects of MSCs on T1DM treatment, indicating a novel role of Wip1 in MSCs immunoregulation properties.
Highlights
Type 1 diabetes mellitus (T1DM), an autoimmune disease induced by multiple factors, causes pancreatic infiltration of T lymphocyte and destruction of β islet cells, which leads to a significant decline in insulin release [1,2,3]
We found that BST2 contributed to the high expression of interferon-α (IFN-α) in Wild-type p53-induce phosphatase 1 (Wip1)−/−mesenchymal stem cells (MSCs), which was an important factor in the pathogenesis of T1DM
Official journal of CDDpress bone fragments and adhered to the flask 48 h (Fig. 1A). These Wip1 interacted with BST2 adherent cells could be readily expanded in vitro by successive To investigate the involvement of Wip1 in MSCs immunomoducycles of trypsinization, seeding, and culture every 3 days without visible morphologic alteration (Fig. 1B, C)
Summary
Type 1 diabetes mellitus (T1DM), an autoimmune disease induced by multiple factors, causes pancreatic infiltration of T lymphocyte and destruction of β islet cells, which leads to a significant decline in insulin release [1,2,3]. It has been reported to be closely associated with tumorigenesis, cell proliferation, as well as development and aging processes [7]. It played important role in regulating the function of immune cells [8,9,10]. Wip could regulate islet cell proliferation and regeneration through modulating the p38 MAPK pathway [14]. These indicated Wip was essential for the biological characteristics of MSCs and islet cells. The effects of Wip on the immunomodulatory function of MSCs need to elucidation
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