期刊
CELL AND BIOSCIENCE
卷 10, 期 1, 页码 -出版社
BMC
DOI: 10.1186/s13578-020-00428-w
关键词
MSCs; SHP1; Immunosuppression; Hepatitis
资金
- National Natural Science of China [81702775, 81861138015, 31771641, 31961133024, 31601106, 81530043, 81571612]
- National Key R&D Program of China [2018YFA0107500, 2018YFC1704300]
- Scientific Innovation Project of the Chinese Academy of Sciences [XDA16020403]
- Ministry of Foreign Affairs and International Cooperation Italy-China Science and Technology Cooperation [PGR00961]
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.
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