T-Cell-Intrinsic Receptor Interacting Protein 2 Regulates Pathogenic T Helper 17 Cell Differentiation.
T-Cell-Intrinsic Receptor Interacting Protein 2 Regulates Pathogenic T Helper 17 Cell Differentiation.
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DOI：
10.1016/j.immuni.2018.08.022
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发表时间：
2018-11-20
期刊：
影响因子：
32.4
通讯作者：
Arditi M
中科院分区：
文献类型：
--
作者：
Shimada K;Porritt RA;Markman JL;O'Rourke JG;Wakita D;Noval Rivas M;Ogawa C;Kozhaya L;Martins GA;Unutmaz D;Baloh RH;Crother TR;Chen S;Arditi M
受体相互作用蛋白2（RIP 2）在感知细胞内病原体中起作用，但其在T细胞中的功能尚不清楚。我们发现，在肺炎衣原体肺部感染过程中，CD 4 + T细胞中RIP 2的缺乏导致慢性和严重的白细胞介素-17A介导的炎症，感染小鼠肺部辅助性T细胞-17（Th 17）形成增加，动脉粥样硬化加速，以及更严重的实验性自身免疫性脑脊髓炎。虽然RIP 2缺陷导致常规Th 17细胞分化减少，但它导致致病性（p）Th 17细胞分化显著增强，这是RORα转录因子和白细胞介素-1依赖性的，但不依赖于核苷酸寡聚化结构域1和2。RIP 2的过表达导致pTh 17细胞分化的抑制，这是由其CARD结构域介导的作用，并由细胞可渗透的RIP 2 CARD肽表型模仿。我们的数据表明，RIP 2在决定稳态和致病性Th 17细胞应答之间的平衡中具有T细胞内在作用。RIP 2是NOD 1和NOD 2介导的细胞内信号传导的关键衔接分子，以感知骨髓细胞中的病原体和细胞活化。Shimada，Porritt及其同事证明了RIP 2在T细胞内在方式的Th 17细胞调节和分化中的先前未被认识的作用。
Receptor Interacting Protein 2 (RIP2) plays a role in sensing intracellular pathogens, but its function in T cells is unclear. We show that RIP2 deficiency in CD4+ T cells resulted in chronic and severe interleukin-17A mediated inflammation during Chlamydia pneumoniae lung infection, increased T helper-17 (Th17) cell formation in lungs of infected mice, accelerated atherosclerosis, and more severe experimental autoimmune encephalomyelitis. While RIP2 deficiency resulted in reduced conventional Th17 cell differentiation, it led to significantly enhanced differentiation of pathogenic (p)Th17 cells, which was RORα transcription factor and interleukin-1 dependent, but Nucleotide Oligomerization Domain 1 and 2 independent. Overexpression of RIP2 resulted in suppression of pTh17 cell differentiation, an effect mediated by its CARD domain, and phenocopied by a cell permeable RIP2 CARD peptide. Our data suggest that RIP2 has a T cell intrinsic role in determining the balance between homeostatic and pathogenic Th17 cell responses. RIP2 is the key adapter molecule for NOD1 and NOD2 mediated intracellular signaling to sense pathogens and cell activation in myeloid cells. Shimada, Porritt and colleagues demonstrate a previously unappreciated role for RIP2 in Th17 cell regulation and differentiation in a T cell intrinsic manner.
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影响因子：
30.5
作者：
通讯作者：
--
影响因子：
3.1
作者：
Balamayooran, Theivanthiran;Batra, Sanjay;Jeyaseelan, Samithamby
通讯作者：
Jeyaseelan, Samithamby
DOI：
10.4049/jimmunol.1001879
发表时间：
2010-11-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Chen S;Shimada K;Zhang W;Huang G;Crother TR;Arditi M
通讯作者：
Arditi M
影响因子：
64.8
作者：
Keestra-Gounder AM;Byndloss MX;Seyffert N;Young BM;Chávez-Arroyo A;Tsai AY;Cevallos SA;Winter MG;Pham OH;Tiffany CR;de Jong MF;Kerrinnes T;Ravindran R;Luciw PA;McSorley SJ;Bäumler AJ;Tsolis RM
通讯作者：
Tsolis RM
影响因子：
16.6
作者：
Lim S;Kim WJ;Kim YH;Lee S;Koo JH;Lee JA;Yoon H;Kim DH;Park HJ;Kim HM;Lee HG;Yun Kim J;Lee JU;Hun Shin J;Kyun Kim L;Doh J;Kim H;Lee SK;Bothwell ALM;Suh M;Choi JM
通讯作者：
Choi JM