Activation of p38α in T cells regulates the intestinal host defense against attaching and effacing bacterial infections.
Activation of p38α in T cells regulates the intestinal host defense against attaching and effacing bacterial infections.
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DOI：
10.4049/jimmunol.1300908
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发表时间：
2013-09-01
期刊：
影响因子：
--
通讯作者：
Kang YJ
中科院分区：
文献类型：
--
作者：
Shim EJ;Bang BR;Kang SG;Ma J;Otsuka M;Kang J;Stahl M;Han J;Xiao C;Vallance BA;Kang YJ
由附着和消失（A/E）细菌病原体引起的肠道感染可引起严重的结肠炎和血性腹泻。虽然p38α在肠上皮细胞（IEC）中通过调节T细胞募集在促进对A/E细菌的保护中起重要作用，但其对免疫应答的影响仍不清楚。在这项研究中，我们发现T细胞中p38α的激活对于A/E病原体啮齿类柠檬酸杆菌的清除至关重要。在T细胞中缺乏p38α的小鼠，而不是在巨噬细胞或树突状细胞中缺乏p38α的小鼠，清除C.啮齿动物。p38α缺陷的T细胞表达的炎性细胞因子如IFN-γ减少，这进一步减少了IEC表达的炎性细胞因子、趋化因子和抗菌肽，并导致T细胞向感染的结肠中的浸润减少。IFN-γ可激活机体对C.通过增加炎症基因的表达和将T细胞募集到感染部位来抑制啮齿动物感染。因此，p38α通过调节激活IEC中宿主防御途径的炎性细胞因子的表达来促进宿主对A/E病原体感染的防御。
Intestinal infections by attaching and effacing (A/E) bacterial pathogens cause severe colitis and bloody diarrhea. Although p38α in intestine epithelial cells (IEC) plays an important role in promoting protection against A/E bacteria by regulating T cell recruitment, its impact on immune responses remains unclear. In this study, we show that activation of p38α in T cells is critical for the clearance of the A/E pathogen Citrobacter rodentium. Mice deficient of p38α in T cells, but not in macrophages or dendritic cells, were impaired in clearing C. rodentium. Expression of inflammatory cytokines such as IFN-γ by p38α-deficient T cells was reduced, which further reduced the expression of inflammatory cytokines, chemokines and anti-microbial peptide by IECs and led to reduced infiltration of T cells into the infected colon. Administration of IFN-γ activated the mucosal immunity to C. rodentium infection by increasing the expression of inflammation genes and the recruitment of T cells to the site of infection. Thus, p38α contributes to host defense against A/E pathogen infection by regulating the expression of inflammatory cytokines that activate host defense pathways in IECs.
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影响因子：
6.7
作者：
Kang YJ;Otsuka M;van den Berg A;Hong L;Huang Z;Wu X;Zhang DW;Vallance BA;Tobias PS;Han J
通讯作者：
Han J
影响因子：
3.1
作者：
Masuda, Atsuhiro;Yoshida, Masaru;Azuma, Takeshi
通讯作者：
Azuma, Takeshi
影响因子：
20.3
作者：
Jirmanova, Ludmila;Torchia, Maria Letizia Giardino;Ashwell, Jonathan D.
通讯作者：
Ashwell, Jonathan D.
DOI：
10.4049/jimmunol.1001536
发表时间：
2010-10-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Li L;Kim J;Boussiotis VA
通讯作者：
Boussiotis VA
影响因子：
32.4
作者：
Kim YG;Kamada N;Shaw MH;Warner N;Chen GY;Franchi L;Núñez G
通讯作者：
Núñez G