Cargando…
Phosphatase SHP1 impedes mesenchymal stromal cell immunosuppressive capacity modulated by JAK1/STAT3 and P38 signals
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...
Autores principales: | , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2020
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7227316/ https://www.ncbi.nlm.nih.gov/pubmed/32467752 http://dx.doi.org/10.1186/s13578-020-00428-w |
_version_ | 1783534478823522304 |
---|---|
author | Jiang, Menghui Ye, Jiayin Wang, Xuefeng Li, Na Wang, Ying Shi, Yufang |
author_facet | Jiang, Menghui Ye, Jiayin Wang, Xuefeng Li, Na Wang, Ying Shi, Yufang |
author_sort | Jiang, Menghui |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-7227316 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-72273162020-05-27 Phosphatase SHP1 impedes mesenchymal stromal cell immunosuppressive capacity modulated by JAK1/STAT3 and P38 signals Jiang, Menghui Ye, Jiayin Wang, Xuefeng Li, Na Wang, Ying Shi, Yufang Cell Biosci Research 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. BioMed Central 2020-05-14 /pmc/articles/PMC7227316/ /pubmed/32467752 http://dx.doi.org/10.1186/s13578-020-00428-w Text en © The Author(s) 2020 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Jiang, Menghui Ye, Jiayin Wang, Xuefeng Li, Na Wang, Ying Shi, Yufang Phosphatase SHP1 impedes mesenchymal stromal cell immunosuppressive capacity modulated by JAK1/STAT3 and P38 signals |
title | Phosphatase SHP1 impedes mesenchymal stromal cell immunosuppressive capacity modulated by JAK1/STAT3 and P38 signals |
title_full | Phosphatase SHP1 impedes mesenchymal stromal cell immunosuppressive capacity modulated by JAK1/STAT3 and P38 signals |
title_fullStr | Phosphatase SHP1 impedes mesenchymal stromal cell immunosuppressive capacity modulated by JAK1/STAT3 and P38 signals |
title_full_unstemmed | Phosphatase SHP1 impedes mesenchymal stromal cell immunosuppressive capacity modulated by JAK1/STAT3 and P38 signals |
title_short | Phosphatase SHP1 impedes mesenchymal stromal cell immunosuppressive capacity modulated by JAK1/STAT3 and P38 signals |
title_sort | phosphatase shp1 impedes mesenchymal stromal cell immunosuppressive capacity modulated by jak1/stat3 and p38 signals |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7227316/ https://www.ncbi.nlm.nih.gov/pubmed/32467752 http://dx.doi.org/10.1186/s13578-020-00428-w |
work_keys_str_mv | AT jiangmenghui phosphataseshp1impedesmesenchymalstromalcellimmunosuppressivecapacitymodulatedbyjak1stat3andp38signals AT yejiayin phosphataseshp1impedesmesenchymalstromalcellimmunosuppressivecapacitymodulatedbyjak1stat3andp38signals AT wangxuefeng phosphataseshp1impedesmesenchymalstromalcellimmunosuppressivecapacitymodulatedbyjak1stat3andp38signals AT lina phosphataseshp1impedesmesenchymalstromalcellimmunosuppressivecapacitymodulatedbyjak1stat3andp38signals AT wangying phosphataseshp1impedesmesenchymalstromalcellimmunosuppressivecapacitymodulatedbyjak1stat3andp38signals AT shiyufang phosphataseshp1impedesmesenchymalstromalcellimmunosuppressivecapacitymodulatedbyjak1stat3andp38signals |