Phosphatase SHP1 impedes mesenchymal stromal cell immunosuppressive capacity modulated by JAK1/STAT3 and P38 signals
Phosphatase SHP1 impedes mesenchymal stromal cell immunosuppressive capacity modulated by JAK1/STAT3 and P38 signals
复制标题
磷酸酶SHP1阻碍JAK1/STAT3和P38信号调节的间充质基质细胞免疫抑制能力
DOI：
10.1186/s13578-020-00428-w
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发表时间：
2020-05-14
影响因子：
7.5
通讯作者：
Shi, Yufang
中科院分区：
文献类型：
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作者：
Jiang, Menghui;Ye, Jiayin;Shi, Yufang
背景间充质基质细胞（Mesenchymal stromal cells，MSCs）是存在于多种组织中的多种基质细胞，已被应用于动物模型和临床试验中，通过强大的免疫抑制能力治疗免疫疾病。我们以前的报告表明，MSC免疫抑制不是内在的，而是在联合炎性细胞因子治疗后获得的。然而，在MSC immunomodulation.ResultsIn的研究中，我们报告，MSC来自活motheaten（mev）小鼠，缺乏SH 2结构域含磷酸酶-1（SHP 1）的详细分子机制的理解仍然不完整，表现出显着增加抑制作用的活化脾细胞增殖。因此，当MSC与联合炎性细胞因子处理时，SHP 1缺陷型MSC与野生型MSC相比产生显著更多的iNOS表达。SHP 1可抑制JAK 1/STAT 3和P38信号的磷酸化。采用刀豆球蛋白A（ConA）诱导的肝损伤动物模型，研究SHP 1在体内调控MSC治疗效应中的作用。与体外结果一致，SHP 1缺陷的MSC表现出显着更有效的保护ConA诱导的肝炎，相比WT MSCs. ConclusionTogether，我们的研究揭示了一个可能的作用，SHP 1在调节MSC免疫抑制JAK 1/STAT 3和P38信号。
BackgroundMesenchymal 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.ResultsIn the study, we report that MSCs derived fromviable motheaten(mev) 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.ConclusionTaken together, our study reveals a possible role for SHP1 in modulation of MSC immunosuppression regulated by JAK1/STAT3 and P38 signals.