Mesenchymal stem cells alleviate idiopathic pneumonia syndrome by modulating T cell function through CCR2-CCL2 axis.
Mesenchymal stem cells alleviate idiopathic pneumonia syndrome by modulating T cell function through CCR2-CCL2 axis.
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DOI：
10.1186/s13287-021-02459-7
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发表时间：
2021-07-02
影响因子：
7.5
通讯作者：
Ren H
中科院分区：
文献类型：
--
作者：
Cao M;Liu H;Dong Y;Liu W;Yu Z;Wang Q;Wang Q;Liang Z;Li Y;Ren H
特发性肺炎综合征（IPS）是异基因造血干细胞移植（allo-HSCT）后的一种非感染性致死性并发症，其特征是肺内大量白细胞浸润和弥漫性肺损伤。传统的免疫抑制治疗IPS的疗效差。目前还没有安全有效的治疗方法，正在探索中。我们前期的研究表明间充质干细胞（mesenchymal stem cells，MSCs）可以缓解IPS，但其机制尚不清楚。将预活化的T细胞与MSCs体外共培养，观察CCR 2-CCL 2轴的变化。通过建立IPS小鼠模型并给予MSCs进一步验证体外实验的结果。预活化T细胞与MSC在体外共培养调节CCR 2-CCL 2轴，导致静止T细胞和向CCR 2 + CD 4 + T细胞亚群极化。阻断CCR 2-CCL 2相互作用消除了MSC的免疫调节作用，导致T细胞的重新活化和向CCR 2 + CD 4 + T细胞极化的部分逆转。在IPS小鼠模型中，应用MSC延长了小鼠的存活时间，减少了病理损伤和T细胞向肺组织的浸润。在用MSC处理的肺中观察到CCR 2-CCL 2轴的活化和CCR 2 + CD 4 + T细胞的产生。在MSC处理的小鼠中，通过施用CCR 2或CCL 2拮抗剂，MSC对IPS的预防作用显著减弱。我们证明了CCR 2-CCL 2轴在调节T细胞功能中的重要作用，这是MSC对IPS的预防作用的机制之一。在线版本包含补充材料，可通过10.1186/s13287-021-02459-7获得。
Idiopathic pneumonia syndrome (IPS) is a non-infectious fatal complication characterized by a massive infiltration of leukocytes in lungs and diffuse pulmonary injury after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Conventional immunosuppressive treatments for IPS have poor therapeutic effects. Safe and effective treatments are not yet available and under explorations. Our previous study demonstrated that mesenchymal stem cells (MSCs) can alleviate IPS, but the mechanisms remain unclear. Co-cultured pre-activated T cells and MSCs in vitro to observe the changes in the CCR2-CCL2 axis. By establishing an IPS mouse model and administering MSCs to further verify the results of in vitro experiments. Co-culture of pre-activated T cells with MSCs in vitro modulated the CCR2-CCL2 axis, resulting in quiescent T cells and polarization toward CCR2+CD4+ T cell subsets. Blocking CCR2-CCL2 interaction abolished the immunoregulatory effect of MSCs, leading to re-activation of T cells and partial reversion of polarizing toward CCR2+CD4+ T cells. In IPS mouse model, application of MSCs prolonged the survival and reduced the pathological damage and T cell infiltration into lung tissue. Activation of CCR2-CCL2 axis and production of CCR2+CD4+ T cells were observed in the lungs treated with MSCs. The prophylactic effect of MSCs on IPS was significantly attenuated by the administration of CCR2 or CCL2 antagonist in MSC-treated mice. We demonstrated an important role of CCR2-CCL2 axis in modulating T cell function which is one of the mechanisms of the prophylactic effect of MSCs on IPS. The online version contains supplementary material available at 10.1186/s13287-021-02459-7.
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影响因子：
6.1
作者：
Seok, Su Jin;Lee, Eun Soo;Chung, Choon Hee
通讯作者：
Chung, Choon Hee
影响因子：
1.3
作者：
Cooke, KR
通讯作者：
Cooke, KR
CCL2缺乏间充质干细胞无法与T细胞建立长期接触，并且不再改善狼疮症状。
影响因子：
4.6
作者：
Lee HK;Kim HS;Kim JS;Kim YG;Park KH;Lee JH;Kim KH;Chang IY;Bae SC;Kim Y;Hong JT;Kehrl JH;Han SB
通讯作者：
Han SB
影响因子：
3.9
作者：
Joo, Sun-Young;Cho, Kyung-Ah;Ryu, Kyung-Ha
通讯作者：
Ryu, Kyung-Ha
影响因子：
24.3
作者：
Raghu, Ganesh;Martinez, Fernando J.;Barnathan, Elliot S.
通讯作者：
Barnathan, Elliot S.