Abstract
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.
Highlights
Frontiers in Immunology The interaction between intestinal microbiome and host immunity plays a critical role in various
We show that mucosal classical dendritic cells defined by the transcription factor Zbtb46 predominantly express CD103
By analyzing DC subpopulations in lamina propria, we found that classical dendritic cells (cDCs) (CD11c+CD103+) were
Summary
Received: 03 February 2018 Accepted: 01 May 2018 Published: 16 May 2018 autoimmune diseases, including Crohn’s disease [1, 2]. Microbial nucleic acid belongs to pathogenassociated molecular patterns that can be recognized by specific sensors in dendritic cells to activate adaptive immunity [3, 4]. (2018) Stimulator of Interferon Genes in Classical Dendritic Cells Controls Mucosal Th17. Responses to Cyclic Dinucleotides for Host Defenses Against Microbial Infections in Gut. Front. C-di-GMP is recognized by stimulator of interferon genes (STING) that leads to IRF3 or NF-κB activation [6,7,8]. Mucosal cDCs induce Th17 generation through a STING-dependent recognition of foreign cyclic dinucleotides. STINGtriggered mucosal Th17 responses can prevent immune evasion of enteroinvasive pathogens and are crucial for host antimicrobial defenses in gut. All animal experiments in this study were undertaken when mice were 6–10 weeks old with protocols approved by the Institutional Subcommittee on Research Animal Care at Nanjing University
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