Phosphatase SHP1 Impedes Mesenchymal Stromal Cell Immunosuppressive Capacity Modulated by JAK1/STAT3 and P38 Signals

Overview

Journal Cell Biosci

Publisher Biomed Central

Specialty Biology

Date 2020 May 30

PMID 32467752

Citations 6

Authors

Menghui Jiang

Jiayin Ye

Xuefeng Wang

Na Li

Ying Wang

Yufang Shi

Affiliations

Soon will be listed here.

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 ( ) 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.

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