IL-23 plays a key role in Helicobacter hepaticus-induced T cell-dependent colitis.
Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract that is caused in part by a dysregulated immune response to the intestinal flora. The common interleukin (IL)-12/IL-23p40 subunit is thought to be critical for the pathogenesis of IBD. We have analyzed the role of IL-12 versus IL-23 in two models of Helicobacter hepaticus-triggered T cell-dependent colitis, one involving anti-IL-10R monoclonal antibody treatment of infected T cell-sufficient hosts, and the other involving CD4+ T cell transfer into infected Rag-/- recipients. Our data demonstrate that IL-23 and not IL-12 is essential for the development of maximal intestinal disease. Although IL-23 has been implicated in the differentiation of IL-17-producing CD4+ T cells that alone are sufficient to induce autoimmune tissue reactivity, our results instead support a model in which IL-23 drives both interferon gamma and IL-17 responses that together synergize to trigger severe intestinal inflammation.
Kullberg
Marika C
MC
Immunobiology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Disease, National Institutes of Health, Bethesda, MD 20892, USA. mk512@york.ac.uk
Jankovic
Dragana
D
Feng
Carl G
CG
Hue
Sophie
S
Gorelick
Peter L
PL
McKenzie
Brent S
BS
Cua
Daniel J
DJ
Powrie
Fiona
F
Cheever
Allen W
AW
Maloy
Kevin J
KJ
Sher
Alan
A
D000818:Animals; D002478:Cells, Cultured; D003092:Colitis / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology*; D005260:Female; D016481:Helicobacter Infections / Q000276:immunology* / Q000378:metabolism; D044923:Helicobacter hepaticus / Q000276:immunology*; D053765:Interleukin-12 Subunit p35 / Q000172:deficiency / Q000235:genetics; D053759:Interleukin-23 / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053701:Receptors, Interleukin-10 / Q000037:antagonists & inhibitors / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
D053765:Interleukin-12 Subunit p35; D053759:Interleukin-23; D053701:Receptors, Interleukin-10