Innate and Adaptive interleukin-22 Protects Mice From Inflammatory Bowel Disease

Immunity. 2008 Dec 19;29(6):947-57. doi: 10.1016/j.immuni.2008.11.003.

Abstract

Inflammatory bowel disease (IBD) is a chronic inflammatory disease thought to be mediated by dysfunctional innate and/or adaptive immunity. This aberrant immune response leads to the secretion of harmful cytokines that destroy the epithelium of the gastrointestinal tract and thus cause further inflammation. Interleukin-22 (IL-22) is a T helper 17 (Th17) T cell-associated cytokine that is bifunctional in that it has both proinflammatory and protective effects on tissues depending on the inflammatory context. We show herein that IL-22 protected mice from IBD. Interestingly, not only was this protection mediated by CD4+ T cells, but IL-22-expressing natural killer (NK) cells also conferred protection. In addition, IL-22 expression was differentially regulated between NK cell subsets. Thus, both the innate and adaptive immune responses have developed protective mechanisms to counteract the damaging effects of inflammation on tissues.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / metabolism
  • Cell Line
  • Colitis / genetics
  • Colitis / immunology
  • Colitis / pathology
  • Colon / immunology
  • Cytokines / immunology*
  • Cytokines / metabolism
  • Disease Models, Animal
  • Homeodomain Proteins / genetics
  • Humans
  • Immunity, Active
  • Immunity, Innate
  • Inflammatory Bowel Diseases / genetics
  • Inflammatory Bowel Diseases / immunology*
  • Inflammatory Bowel Diseases / pathology
  • Interleukins / genetics
  • Interleukins / immunology*
  • Interleukins / metabolism
  • Killer Cells, Natural / immunology*
  • Killer Cells, Natural / metabolism
  • Mice
  • Mice, Knockout
  • Recombinant Proteins / genetics
  • Recombinant Proteins / immunology
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocyte Subsets / metabolism

Substances

  • Cytokines
  • Homeodomain Proteins
  • Interleukins
  • Recombinant Proteins
  • RAG-1 protein
  • interleukin-22