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 (Lck(cre)IL-4Rα(-/lox)). We also generated mice with B cells that did not express IL-4Rα (mb1(cre)IL-4Rα(-/lox)) and studied induction of colitis. RESULTS: Lck(cre)IL-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 Lck(cre)IL-4Rα(-/lox) mice restored their susceptibility to colitis. In contrast, Lck(cre)IL-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. Mb1(cre)IL-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.
BACKGROUND & AIMS: Induction of colitis in mice by administration of oxazolone is mediated by T-helper (Th) 2 cells and has features of humanulcerative 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 (Lck(cre)IL-4Rα(-/lox)). We also generated mice with B cells that did not express IL-4Rα (mb1(cre)IL-4Rα(-/lox)) and studied induction of colitis. RESULTS:Lck(cre)IL-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 Lck(cre)IL-4Rα(-/lox) mice restored their susceptibility to colitis. In contrast, Lck(cre)IL-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. Mb1(cre)IL-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.
Authors: Stefan Wirtz; Vanessa Popp; Markus Kindermann; Katharina Gerlach; Benno Weigmann; Stefan Fichtner-Feigl; Markus F Neurath Journal: Nat Protoc Date: 2017-06-01 Impact factor: 13.491
Authors: J Cosín-Roger; D Ortiz-Masiá; S Calatayud; C Hernández; J V Esplugues; M D Barrachina Journal: Mucosal Immunol Date: 2015-11-25 Impact factor: 7.313
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Authors: A Yokota-Nakatsuma; H Takeuchi; Y Ohoka; C Kato; S-Y Song; T Hoshino; H Yagita; T Ohteki; M Iwata Journal: Mucosal Immunol Date: 2013-11-13 Impact factor: 7.313