Phosphatase SHP1 impedes mesenchymal stromal cell immunosuppressive capacity modulated by JAK1/STAT3 and P38 signals

Menghui Jiang; Jiayin Ye; Xuefeng Wang; Na Li; Ying Wang; Yufang Shi

doi:10.1186/s13578-020-00428-w

Phosphatase SHP1 impedes mesenchymal stromal cell immunosuppressive capacity modulated by JAK1/STAT3 and P38 signals

Cell Biosci. 2020 May 14:10:65. doi: 10.1186/s13578-020-00428-w. eCollection 2020.

Authors

Menghui Jiang¹, Jiayin Ye², Xuefeng Wang³, Na Li², Ying Wang², Yufang Shi^{1

3

2}

Affiliations

¹ 1School of Public Health, Qingdao University, Qingdao, China.
² 3Key Laboratory of Stem Cell Biology, Shanghai Institute of Nutrition and Health, Chinese Academy of Sciences, Shanghai, 200031 China.
³ 2The Third Affiliated Hospital of Soochow University, Institutes for Translational Medicine, Soochow University, Suzhou, China.

Abstract

Background: Mesenchymal stromal cells (MSCs) are multiple stromal cells existing in various tissues and have already been employed in animal models and clinical trials to treat immune disorders through potent immunosuppressive capacity. Our previous reports have suggested that MSC immunosuppression is not intrinsic but is acquired upon combined inflammatory cytokine treatment. However, the understanding of detailed molecular mechanisms involved in MSC immunomodulation remains incomplete.

Results: In the study, we report that MSCs derived from viable motheaten (me ^v ) mice, with deficiency in SH2 domain-containing phosphatase-1 (SHP1), exhibited remarkable increased suppressive effect on activated splenocyte proliferation. Consistently, when MSCs were treated with combined inflammatory cytokines, SHP1-deficient MSCs produced dramatically more iNOS expression compared with wild-type MSCs. SHP1 was found to suppress the phosphorylation of JAK1/STAT3 and P38 signals. The classical animal model of concanavalin A (ConA)-induced liver injury was applied to examine the role of SHP1 in modulation MSC-therapeutic effect in vivo. Consistent with the results in vitro, SHP1-deficient MSCs exhibited dramatically more effective protection against ConA-induced hepatitis, compared to WT MSCs.

Conclusion: Taken together, our study reveals a possible role for SHP1 in modulation of MSC immunosuppression regulated by JAK1/STAT3 and P38 signals.

Keywords: Hepatitis; Immunosuppression; MSCs; SHP1.