Wip1 regulates the immunomodulatory effects of murine mesenchymal stem cells in type 1 diabetes mellitus via targeting IFN-α/BST2.

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.

• Authors: Na Zhou, Weijiang Liu, Wei Zhang, Yuanlin Liu, Xue Li, Yang Wang, Rongxiu Zheng, Yi Zhang
• Journal: Cell death discovery (Cell Death Discov) Vol. 7 Issue 1 Pg. 326 (Oct 29 2021) ISSN: 2058-7716 [Print] United States
• PMID: 34716317 (Publication Type: Journal Article)
• Copyright: © 2021. The Author(s).