Stimulator of Interferon Genes in Classical Dendritic Cells Controls Mucosal Th17 Responses to Cyclic Dinucleotides for Host Defenses Against Microbial Infections in Gut

Frontiers in Immunology

Jie Wu¹  Xiuwen Wu¹  Qiongyuan Hu¹  Qiu Rao³  Qiuyuan Xia³  Wenxian Guan⁴  Song Liu⁴  Meng Wang⁴  Feng Sun⁴ 

[1] Department of General Surgery, Jinling Hospital, Nanjing, China;Department of General Surgery, Nanjing Drum Tower Hospital, Nanjing, China;Department of Pathology, Jinling Hospital, Nanjing, China;School of Medicine, Nanjing University, Nanjing, China;

关键词: stimulator of interferon genes;    dendritic cell;    Th17;    Salmonella;    cyclic dinucleotides;    Crohn’s disease;   

DOI  :  10.3389/fimmu.2018.01085

来源: DOAJ

【 摘 要 】

Cyclic dinucleotides are bacterial signal transducers that bind to host intracellular protein, stimulator of interferon genes (STING) encoded by Tmem173. In this study, we demonstrate that STING triggers adaptive immune responses that control Th17 differentiation. Cyclic dinucleotides recognition enables classical dendritic cells (cDCs) that predominantly express CD103 to induce Th17 lymphocytes in an IL-6/IL-1β-dependent manner in gut. STING expression in human lamina propria is associated with the severity of mucosal inflammation and clinical disease activity in patients with Crohn’s disease. Mice deficient in Tmem173 fail to mount Th17 responses to cyclic dinucleotides or prevent immune evasion of enteroinvasive pathogens. In summary, STING in mucosal cDCs controls Th17 subspecification that is essential for host defenses against microbial infection in gut-associated immune system.

【 授权许可】

Unknown