c-Rel Is Essential for the Development of Innate and T Cell-Induced Colitis

• Published in: The Journal of immunology (1950) 2008-06, Vol.180 (12), p.8118-8125
• Main Authors: Wang, Yanyan, Rickman, Barry H, Poutahidis, Theofilos, Schlieper, Katherine, Jackson, Erin A, Erdman, Susan E, Fox, James G, Horwitz, Bruce H
• Format: Article
• Language: English
• Subjects: Animals; Chronic Disease; Colitis - immunology; Colitis - metabolism; Colitis - microbiology; Cyclin-Dependent Kinase Inhibitor p19 - biosynthesis; Cytokines - biosynthesis; Cytokines - deficiency; Cytokines - physiology; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; Helicobacter hepaticus; Helicobacter hepaticus - immunology; Helicobacter Infections - genetics; Helicobacter Infections - immunology; Helicobacter Infections - microbiology; Immunity, Innate - genetics; Inflammation Mediators - metabolism; Inflammation Mediators - physiology; Interleukin-10 - biosynthesis; Interleukin-10 - deficiency; Interleukin-12 - biosynthesis; Interleukin-12 - deficiency; Interleukin-23 - biosynthesis; Interleukin-23 - deficiency; Mice; Mice, Knockout; Multigene Family - immunology; Proto-Oncogene Proteins c-rel - deficiency; Proto-Oncogene Proteins c-rel - genetics; Proto-Oncogene Proteins c-rel - physiology; Receptors, G-Protein-Coupled - biosynthesis; T-Lymphocyte Subsets - immunology; Up-Regulation - genetics; Up-Regulation - immunology
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.180.12.8118

Inflammatory bowel disease is a chronic inflammatory response of the gastrointestinal tract mediated in part by an aberrant response to intestinal microflora. Expression of IL-23 subunits p40 and p19 within cells of the innate immune system plays a central role in the development of lower bowel inflammation in response inflammatory challenge. The NF-kappaB subunit c-Rel can regulate expression of IL-12/23 subunits suggesting that it could have a critical role in mediating the development of chronic inflammation within the lower bowel. In this study, we have analyzed the role of c-Rel within the innate immune system in the development of lower bowel inflammation, in two well-studied models of murine colitis. We have found that the absence of c-Rel significantly impaired the ability of Helicobacter hepaticus to induce colitis upon infection of RAG-2-deficient mice, and ameliorated the ability of CD4(+)CD45RB(high) T cells to induce disease upon adoptive transfer into RAG-deficient mice. The absence of c-Rel interfered with the expression of IL-12/23 subunits both in cultured primary macrophages and within the colon. Thus, c-Rel plays a critical role in regulating the innate inflammatory response to microflora within the lower bowel, likely through its ability to modulate expression of IL-12/23 family members.