Phosphatase SHP1 impedes mesenchymal stromal cell immunosuppressive capacity modulated by JAK1/STAT3 and P38 signals
| Autor: | Na Li, Xuefeng Wang, Ying Wang, Menghui Jiang, Yufang Shi, Jiayin Ye |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Stromal cell lcsh:Biotechnology medicine.medical_treatment SHP1 MSCs General Biochemistry Genetics and Molecular Biology Proinflammatory cytokine Hepatitis lcsh:Biochemistry 03 medical and health sciences 0302 clinical medicine Immune system In vivo lcsh:TP248.13-248.65 medicine Splenocyte lcsh:QD415-436 lcsh:QH301-705.5 Chemistry Research Mesenchymal stem cell 030104 developmental biology Cytokine lcsh:Biology (General) Cancer research Stem cell 030217 neurology & neurosurgery Immunosuppression |
| Zdroj: | Cell & Bioscience Cell & Bioscience, Vol 10, Iss 1, Pp 1-10 (2020) |
| ISSN: | 2045-3701 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full text from SpringerLink