2. Academic Validation
  3. Enterobacter ludwigii protects DSS-induced colitis through choline-mediated immune tolerance

Enterobacter ludwigii protects DSS-induced colitis through choline-mediated immune tolerance

  • Cell Rep. 2022 Aug 30;40(9):111308. doi: 10.1016/j.celrep.2022.111308.
Qianqian Li 1,  Xuan Sun 1,  Kaiyuan Yu 1,  Junqiang Lv 1,  Chunhui Miao 1,  Jianming Yang 1,  Song Wang 2,  Zheng Fu 3,  Yamin Sun 4,  Hong Zhang 1,  Zhi-Song Zhang 5,  Evan T Keller 6,  Zhi Yao 7,  Quan Wang 8
Affiliations

Affiliations

  • 1 Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), Tianjin Institute of Immunology, Tianjin Institute of Urology, Department of Immunology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China.
  • 2 Tianjin Kangzhe Pharmaceutical Technology Development Company, Ltd., Tianjin 300042, China.
  • 3 Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), Tianjin Institute of Immunology, Tianjin Institute of Urology, Department of Immunology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China; Tianjin Kangzhe Pharmaceutical Technology Development Company, Ltd., Tianjin 300042, China.
  • 4 Tianjin Biochip Corporation, Tianjin, China.
  • 5 State Key Laboratory of Medicinal Chemical Biology and College of Pharmacy, Collaborative Innovation Center for Biotherapy, and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 300350, China.
  • 6 Department of Urology, University of Michigan, Ann Arbor, MI, USA; Biointerfaces Institute, University of Michigan, Ann Arbor, MI, USA.
  • 7 Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), Tianjin Institute of Immunology, Tianjin Institute of Urology, Department of Immunology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China; The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, Tianjin Medical University, Tianjin 300070, China. Electronic address: [email protected].
  • 8 Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), Tianjin Institute of Immunology, Tianjin Institute of Urology, Department of Immunology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China; The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, Tianjin Medical University, Tianjin 300070, China. Electronic address: [email protected].
PMID: 36044853 DOI: 10.1016/j.celrep.2022.111308
Abstract

Commensal intestinal bacteria play key roles in regulating host immune tolerance; however, Bacterial strains and related metabolites directly involved in this regulation are largely unknown. Here, using a mouse model of dextran sulfate sodium (DSS)-induced colitis combined with different Antibiotic treatment, Enterobacter ludwigii, abundant in microbiota of mice treated with metronidazole, is screened out to have prophylactic and therapeutic effects on DSS-induced colitis with or without the presence of complex intestinal bacteria. E. ludwigii is found to induce CD103+DC and regulatory T (Treg)-mediated immune tolerance for colitis remission using in vitro and in vivo experiments. Moreover, choline, one metabolite of E. ludwigii, is identified to increase dendritic cells' (DCs) immune tolerance to promote Treg differentiation. E. ludwigii is found to induce DCs' immune tolerance ability for Treg differentiation through choline and α7nAChR-mediated retinoic acid (RA) and transforming growth factor beta (TGF-β) upregulation, resulting in protecting mice against DSS-induced colitis. This study suggests potential therapeutic approaches for inflammatory bowel diseases (IBDs).

Keywords

CD103(+)DC; CP: Immunology; E. ludwigii; Tregs; choline; colitis.

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