(A) IRF4 expression was analyzed by immunofluorescence (red) in oxazolone colitis. IRF4^–/– mice served as negative control (upper panel). Colitic WT mice had many IRF4-positive cells in the lamina propria (lower panel) as compared with untreated WT mice (middle panel). Original magnification, ×400. *P < 0.05. (B) WT (n = 8) and IRF4-deficient mice (n = 11) were treated by rectal administration of oxazolone following prior sensitization. WT (IRF4^+/+) mice lost significantly more weight as compared with oxazolone-treated IRF4^–/– mice, untreated WT mice (n = 5), or untreated knockout mice (n = 3). **P < 0.01 on days 3 and 4. (C) IRF4-deficient mice showed a significantly reduced endoscopic score. (D) Representative endoscopic pictures from each group are shown. (E) Histological scoring revealed a significantly higher degree of inflammation in oxazolone-treated WT mice as compared with IRF4^–/– mice. Data are given as mean values ± SEM (IRF4^+/+ plus oxazolone, n = 8; IRF4^–/– plus oxazolone, n = 11; IRF4^+/+, n = 5; IRF4^–/–, n = 3). (F) Histological findings showed moderate to severe inflammation in WT mice, whereas little or no inflammation was noted in IRF4^–/– mice. (G) In further studies, chronic oxazolone colitis was evaluated. Mice were treated 3 times by intrarectal application of oxazolone and evaluated on day 21. A more severe colitis activity was induced in WT mice (n = 5) as compared with IRF4^–/– mice (n = 5) (F). This was underlined by differences (**P < 0.01) in the histologic score between both groups (G). (H) Representative histologic pictures from each group are shown. Original magnification, ×100.