The transcription factor IFN regulatory factor–4 controls experimental colitis in mice via T cell–derived IL-6
J. Clin. Invest. Jonas Mudter, et al. 118:2415 doi:10.1172/JCI33227 [
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Figure 2Abrogation of oxazolone-induced colitis in IRF4-deficient mice. (
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.