c-Rel is Essential for the Development of Innate and T cell-Induced Colitis1

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 infl...

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Veröffentlicht in:The Journal of immunology (1950) 2008-06, Vol.180 (12), p.8118-8125
Hauptverfasser: Wang, Yanyan, Rickman, Barry H., Poutahidis, Theofilos, Schlieper, Katherine, Jackson, Erin A., Erdman, Susan E., Fox, James G., Horwitz, Bruce H.
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Sprache:eng
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Zusammenfassung: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-κB 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. Here 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 H. 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.
ISSN:0022-1767
1550-6606