Mucosa-associated microbiota drives pathogenic functions in IBD-derived intestinal iNKT cells

Life Sci Alliance. 2019 Feb 13;2(1):e201800229. doi: 10.26508/lsa.201800229. Print 2019 Feb.


Inflammatory bowel disease (IBD) pathogenesis has been linked to the aberrant activation of the Gut-associated lymphoid tissues against components of the intestinal microbiota. Although the contribution of CD4+ T helper cells to inflammatory processes is being increasingly acknowledged, the functional engagement of human invariant natural killer T (iNKT) cells is still poorly defined. Here, we evaluated the functional characteristics of intestinal iNKT cells during IBD pathogenesis and to exploit the role of mucosa-associated microbiota recognition in triggering iNKT cells' pro-inflammatory responses in vivo. Lamina propria iNKT cells, isolated from surgical specimens of active ulcerative colitis and Crohn's disease patients and non-IBD donors, were phenotypically and functionally analyzed ex vivo, and stable cell lines and clones were generated for in vitro functional assays. iNKT cells expressing a pro-inflammatory cytokine profile were enriched in the lamina propria of IBD patients, and their exposure to the mucosa-associated microbiota drives pro-inflammatory activation, inducing direct pathogenic activities against the epithelial barrier integrity. These observations suggest that iNKT cell pro-inflammatory functions may contribute to the fuelling of intestinal inflammation in IBD patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Animals
  • CD4 Antigens / metabolism
  • Caco-2 Cells
  • Clone Cells / metabolism
  • Coculture Techniques
  • Colitis, Ulcerative / chemically induced
  • Colitis, Ulcerative / microbiology*
  • Colitis, Ulcerative / pathology
  • Colitis, Ulcerative / surgery
  • Crohn Disease / microbiology*
  • Crohn Disease / surgery
  • Cytokines / metabolism
  • Dextran Sulfate / pharmacology
  • Disease Models, Animal
  • Female
  • Gastrointestinal Microbiome*
  • Humans
  • Inflammation / immunology
  • Inflammation / metabolism
  • Intestinal Mucosa / immunology
  • Intestinal Mucosa / microbiology*
  • Lymphocyte Activation / immunology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Middle Aged
  • NK Cell Lectin-Like Receptor Subfamily B / metabolism
  • Natural Killer T-Cells / immunology
  • Natural Killer T-Cells / metabolism*
  • Phenotype


  • CD4 Antigens
  • Cytokines
  • KLRB1 protein, human
  • NK Cell Lectin-Like Receptor Subfamily B
  • Dextran Sulfate