P21 activated kinase-1 (PAK1) in macrophages is required for promotion of Th17 cell response during helminth infection.
P21 activated kinase-1 (PAK1) in macrophages is required for promotion of Th17 cell response during helminth infection.
复制标题
巨噬细胞中的 P21 激活激酶 1 (PAK1) 是蠕虫感染过程中促进 Th17 细胞反应所必需的
DOI：
10.1111/jcmm.16050
复制
发表时间：
2020-12
影响因子：
5.3
通讯作者：
Ji MJ
中科院分区：
文献类型：
--
作者：
Chang H;He KY;Li C;Ni YY;Li MN;Chen L;Hou M;Zhou Z;Xu ZP;Ji MJ
CD 4 +T细胞分化成不同的功能效应子和抑制性亚群是由抗原识别时存在的不同细胞因子线索促进的。维持辅助性T细胞17（Th 17）和调节性T细胞（Treg）之间的平衡对于控制肝脏疾病的免疫发病机制至关重要。在这里，通过使用蠕虫日本血吸虫（S japonicum）感染的小鼠模型，我们发现，肝P21激活激酶1（PAK 1）的mRNA水平，肌动蛋白细胞骨架，粘附和细胞运动的关键调节剂，显着增加，并与肝病理学的发展在日本血吸虫感染。此外，PAK 1缺陷小鼠易于抑制Th 17细胞应答，但增加Treg细胞。此外，PAK 1通过促进NF-κB依赖性途径中的IRF 1核转位增强巨噬细胞活化，从而通过诱导IL-6产生促进Th 17细胞分化。这些发现强调了PAK 1在巨噬细胞命运决定中的重要性，并表明PAK 1/IRF 1轴依赖性免疫调节可以改善某些基于T细胞的免疫病理学。
CD4+T cells differentiate into distinct functional effector and inhibitory subsets are facilitated by distinct cytokine cues present at the time of antigen recognition. Maintaining a balance between T helper 17 (Th17) and regulatory T (Treg) cells are critical for the control of the immunopathogenesis of liver diseases. Here, by using the mouse model of helminth Schistosoma japonicum (S japonicum) infection, we show that the hepatic mRNA levels of P21‐activated kinase 1 (PAK1), a key regulator of the actin cytoskeleton, adhesion and cell motility, are significantly increased and associated with the development of liver pathology during S japonicum infection. In addition, PAK1‐deficient mice are prone to suppression of Th17 cell responses but increased Treg cells. Furthermore, PAK1 enhances macrophage activation through promoting IRF1 nuclear translocation in an NF‐κB‐dependent pathway, resulting in promoting Th17 cell differentiation through inducing IL‐6 production. These findings highlight the importance of PAK1 in macrophages fate determination and suggest that PAK1/IRF1 axis‐dependent immunomodulation can ameliorate certain T cell–based immune pathologies.
登录
查看更多内容
影响因子：
6.7
作者：
Girgis NM;Gundra UM;Ward LN;Cabrera M;Frevert U;Loke P
通讯作者：
Loke P
影响因子：
5
作者：
Chang, Ling-Chu;Lin, Ruey-Hseng;Wang, Jih-Pyang
通讯作者：
Wang, Jih-Pyang
影响因子：
4.7
作者：
Asrar, Suhail;Meng, Yanghong;Jia, Zhengping
通讯作者：
Jia, Zhengping
影响因子：
5.3
作者：
Huang, Wayne;Zhou, Zikai;Jia, Zhengping
通讯作者：
Jia, Zhengping
影响因子：
5.5
作者：
Joshi, Amrita D.;Raymond, Tracy;Hogaboam, Cory M.
通讯作者：
Hogaboam, Cory M.