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

Na Zhou; Weijiang Liu; Wei Zhang; Yuanlin Liu; Xue Li; Yang Wang; Rongxiu Zheng; Yi Zhang

doi:10.1038/s41420-021-00728-1

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

Cell Death Discov. 2021 Oct 29;7(1):326. doi: 10.1038/s41420-021-00728-1.

Authors

Na Zhou^#^{1

2}, Weijiang Liu^#¹, Wei Zhang^#³, Yuanlin Liu¹, Xue Li¹, Yang Wang¹, Rongxiu Zheng⁴, Yi Zhang⁵

Affiliations

¹ Department of Experimental Hematology and Biochemistry, Beijing Institute of Radiation Medicine, Beijing, 100850, China.
² Department of Pediatrics, Tianjin Medical University General Hospital, Tianjin, 300052, China.
³ Department of Medical Administration, The Sixth Medical Center of PLA General Hospital, Beijing, 100048, China.
⁴ Department of Pediatrics, Tianjin Medical University General Hospital, Tianjin, 300052, China. rzheng@tmu.edu.cn.
⁵ Department of Experimental Hematology and Biochemistry, Beijing Institute of Radiation Medicine, Beijing, 100850, China. zhangyi612@hotmail.com.

^# Contributed equally.

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.