Ligation of CD180 contributes to endotoxic shock by regulating the accumulation and immunosuppressive activity of myeloid-derived suppressor cells through STAT3
Ligation of CD180 contributes to endotoxic shock by regulating the accumulation and immunosuppressive activity of myeloid-derived suppressor cells through STAT3
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CD180 连接通过 STAT3 调节骨髓源性抑制细胞的积累和免疫抑制活性，从而导致内毒素休克
DOI：
10.1016/j.bbadis.2018.12.013
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发表时间：
2019
影响因子：
6.2
通讯作者：
Xiong Huabao
中科院分区：
文献类型：
--
作者：
Dong Guanjun;Yao Xiaoying;Yan Fenglian;Zhang Hui;Zhu Yuzhen;Yang Yonghong;Shi Hui;Zhang Junfeng;Ning Zhaochen;Wang Cuiling;Cheng Panpan;Hu Yuan;Ma Qun;Dai Jun;Li Zhihua;Li Chunxia;Ming Jiankuo;Li Xuehui;Si Chuanping;Xiong Huabao
骨髓源性抑制细胞（MDSC）在炎症性疾病的发病机制中发挥免疫抑制作用。CD 180是一种TLR样蛋白，可调节免疫细胞的增殖和活化。然而，CD 180在调节MDSC的积累和功能中的作用尚未研究。在这里，我们发现，与未处理的对照组相比，CD 180的表达在MDSC中显著升高，特别是粒细胞MDSC（G-MDSC），来自用脂多糖（LPS）攻击的小鼠。通过抗CD 180抗体连接CD 180不仅通过阻止信号转导和转录激活因子3（STAT 3）的磷酸化来阻断MDSC的扩增，而且通过抑制Arg-1的表达降低了MDSC对M1巨噬细胞极化的免疫抑制活性。CD 180抗体可加重LPS攻击小鼠的病理损伤。此外，注射抗CD 180抗体可抑制LPS攻击小鼠中G-MDSC的积聚，并降低G-MDSC对M1巨噬细胞极化的免疫抑制活性。基于这些发现，我们得出结论，CD 180的连接有助于通过抑制G-MDSC的积累和免疫抑制活性的内毒素休克的发病机制，从而提供了深入了解CD 180在炎症性疾病中的功能。
Myeloid-derived suppressor cells (MDSCs) play an immunosuppressive role in the pathogenesis of inflammatory diseases. CD180, a TLR-like protein, can regulate the proliferation and activation of immune cells. However, the roles of CD180 in regulating the accumulation and function of MDSCs have not been investigated. Here, we found that, compared with non-treated controls, the expression of CD180 was significantly elevated in MDSCs, especially granulocytic MDSCs (G-MDSCs), from mice challenged with lipopolysaccharide (LPS). Ligation of CD180 by the anti-CD180 antibody not only blocked the expansion of MDSCs by preventing the phosphorylation of signal transducer and activator of transcription 3 (STAT3), but also reduced the immunosuppressive activity of MDSCs on M1 macrophage polarization through inhibition of Arg-1 expressionin vitro.In vivostudies showed that injection of anti-CD180 antibody significantly aggravated pathological lesions in mice challenged with LPS. Furthermore, injection of anti-CD180 antibody inhibited the accumulation of G-MDSCs in mice challenged with LPS and reduced the immunosuppressive activity of G-MDSCs on M1 macrophage polarization. Based on these findings, we conclude that ligation of CD180 contributes to the pathogenesis of endotoxic shock by inhibiting the accumulation and immunosuppressive activity of G-MDSCs, thus providing insight into the function of CD180 in inflammatory diseases.