A Gut Microbial Mimic that Hijacks Diabetogenic Autoreactivity to Suppress Colitis

Cell. 2017 Oct 19;171(3):655-667.e17. doi: 10.1016/j.cell.2017.09.022.


The gut microbiota contributes to the development of normal immunity but, when dysregulated, can promote autoimmunity through various non-antigen-specific effects on pathogenic and regulatory lymphocytes. Here, we show that an integrase expressed by several species of the gut microbial genus Bacteroides encodes a low-avidity mimotope of the pancreatic β cell autoantigen islet-specific glucose-6-phosphatase-catalytic-subunit-related protein (IGRP206-214). Studies in germ-free mice monocolonized with integrase-competent, integrase-deficient, and integrase-transgenic Bacteroides demonstrate that the microbial epitope promotes the recruitment of diabetogenic CD8+ T cells to the gut. There, these effectors suppress colitis by targeting microbial antigen-loaded, antigen-presenting cells in an integrin β7-, perforin-, and major histocompatibility complex class I-dependent manner. Like their murine counterparts, human peripheral blood T cells also recognize Bacteroides integrase. These data suggest that gut microbial antigen-specific cytotoxic T cells may have therapeutic value in inflammatory bowel disease and unearth molecular mimicry as a novel mechanism by which the gut microbiota can regulate normal immune homeostasis. PAPERCLIP.

Keywords: Bacteroides Integrase; Cytotoxic T cells; Germ-free mice; Inflammatory bowel disease; Islet-specific glucose 6-phosphatase catalytic subunit-related protein (IGRP); Molecular mimicry.

MeSH terms

  • Adult
  • Animals
  • Autoantigens / immunology*
  • Bacteroides / classification
  • Bacteroides / enzymology
  • Bacteroides / immunology*
  • Colitis / immunology*
  • Colitis / microbiology
  • Female
  • Gastrointestinal Microbiome*
  • Glucose-6-Phosphatase / genetics
  • Glucose-6-Phosphatase / immunology*
  • Humans
  • Lymphoid Tissue / immunology
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred NOD
  • Middle Aged
  • Molecular Mimicry
  • T-Lymphocytes / immunology


  • Autoantigens
  • Glucose-6-Phosphatase
  • G6PC2 protein, human
  • G6pc2 protein, mouse