IL-23 plays a key role in Helicobacter hepaticus–induced T cell–dependent colitis

By M. Kullberg, Dragana Jankovic, C. Feng, S. Hue, P. Gorelick, Brent S. McKenzie, D. Cua, F. Powrie, A. Cheever, K. Maloy and 1 more. Journal of Experimental Medicine, 2006

648 citations recorded by the source corpus.

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 γ and IL-17 responses that together synergize to trigger severe intestinal inflammation.

Subfields: Epidemiology, Genetics

View Paper: https://www.semanticscholar.org/paper/d138565883ffe2b5ccaa5f60abedaa1aa442da00

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Epidemiology

1. Teresa Zelante
2. Paolo Puccetti
3. A. De Luca
4. F. Powrie
5. L. Romani
6. M. Pohin
7. R. Flavell
8. R. Blumberg

In Genetics

1. F. Powrie
2. M. Pohin
3. June L. Round
4. M. Friedrich
5. S. Mazmanian
6. D. Munn

Citations in the corpus

• IL‐23 and the Th17 pathway promote inflammation and impair antifungal immune resistance (2007, background): “As a matter of fact, in experimental Helicobacter hepaticus-induced colitis, IL-23 has clearly been shown to drive both IFN-cand IL-17-producing cells [ 35 ].”
• Inducible Foxp3+ regulatory T-cell development by a commensal bacterium of the intestinal microbiota (2010, background): “Suppression of Thl and Th17 cell responses by Tregs prevents inflammation in experimental models of colitis (7, 8).”
• Biology and Diseases of Mice (2015, neutral): “(2001) , Kullberg et al.”
• IL-22 ameliorates intestinal inflammation in a mouse model of ulcerative colitis. (2008, background): “In contrast, IL-23/IL-17 pathways have recently been shown to play a pathogenic role in experimental CD-like diseases (15, 16, 47, 48).”
• A human colonic commensal promotes colon tumorigenesis via activation of T helper type 17 T cell responses (2009, positive): “Stat3-driven T H 17 responses, characterized by production of IL-17A in mice and humans and driven by IL-23, are crucial in mucosal inflammatory responses in the lung and gut and are implicated in a number of autoimmune disorder”
• Cytokine Networks in the Pathophysiology of Inflammatory Bowel Disease. (2019, positive): “…al., 2006) (not MD-IBD) - anti-IL-23p19 and anti-IL-12p40 ameliorate antiCD40- and Helicobacter hepaticus-induced innate colitis, and Il10 -/- colitis (Kullberg et al., 2006; Uhlig et al., 2006; Yen et al., 2006) anti-IL-12p40 (approved for moderate-to-severe CD) (Feagan et al.,…”