hide
Free keywords:
Immune Regulation; IBD; Inflammatory Bowel Disease; T-Cell Signaling
Abstract:
BACKGROUND & AIMS: Induction of colitis in mice by administration of oxazolone is mediated by T-helper (Th) 2 cells and has features of human ulcerative colitis. We investigated whether activation of interleukin (IL)-4Rα on T and B cells determines their effector functions and mediates oxazolone-induced colitis.
METHODS: We studied induction of colitis with oxazolone in wild-type mice and those with CD4+ T cells that did not express IL-4Rα (LckcreIL-4Rα-/lox). We also generated mice with B cells that did not express IL-4Rα (mb1creIL-4Rα-/lox) and studied induction of colitis.
RESULTS: LckcreIL-4Rα-/lox mice did not develop colitis in response to oxazolone, and their levels of IL-4, IL-13, and immunoglobulin (Ig) E were reduced. Adoptive transfer of naïve, wild-type CD4+ Th cells depleted of natural killer T cells to LckcreIL-4Rα-/lox mice restored their susceptibility to colitis. In contrast, LckcreIL-4Rα-/lox mice maintained their protection against colitis when IL-13-deficient CD4+ T cells were transferred. These findings indicate that development of colitis involves not only natural killer T-cell functions, but also requires IL-13 production by CD4+ T helper cells. Mb1creIL-4Rα-/lox mice, which cannot produce IgE, were also protected against oxazolone-induced colitis. Blocking IgE binding significantly reduced mast cell numbers in colons and protected wild-type BALB/c mice from the onset of colitis.
CONCLUSIONS: IL-4 appears to induce CD4+ Th2 cells to produce IL-13 and B cells to produce IgE, which together mediate oxazolone-induced colitis in mice.
