JCI - The transcription factor IFN regulatory factor–4 controls experimental colitis in mice via T cell

The transcription factor IFN regulatory factor–4 controls experimental colitis in mice via T cell–derived IL-6

Jonas Mudter, Lioubov Amoussina, Mirjam Schenk, Jingling Yu, Anne Brüstle, Benno Weigmann, Raja Atreya, Stefan Wirtz, Christoph Becker, Arthur Hoffman, Imke Atreya, Stefan Biesterfeld, Peter R. Galle, Hans A. Lehr, Stefan Rose-John, Christoph Mueller, Michael Lohoff, Markus F. Neurath

Published in Volume 118, Issue 7

J Clin Invest. 2008; 118(7):2415–2426 doi:10.1172/JCI33227

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Figure 5

Decreased activation of the antiapoptotic IL-6 pathway in IRF4-deficient T cells.

(A) LPMCs from WT and IRF4-deficient mice were cultured with or without anti-CD3/CD28 antibodies. IL-6 production was higher in WT mice as compared with IRF4-deficient mice upon costimulation. (B–D) T cell–enriched LPMCs (B), CD90⁺ LP T cells (C), or splenic T cells (D) were isolated from TNBS-treated mice and stimulated for 2 days. LP cells but not spleen cells from TNBS-treated IRF4-deficient mice produced significantly lower amounts of IL-6 than cells from TNBS-treated WT mice (n = 9–10 mice per group; **P < 0.01) (E) TNBS-treated WT mice exhibited an increased number of IL-6–positive cells (red) in the lamina propria as compared with controls. Original magnification, ×300. (F) IL-6–positive cells were counted in TNBS-treated IRF4^–/– and WT mice (5 HPFs). IL-6–positive cells were increased in TNBS-treated WT mice compared with IRF4-deficient mice. (G) Colonic cryosections were stained using TUNEL assays. There were more positive cells in the colons of TNBS-treated IRF4-knockout mice than in TNBS-treated WT mice (n = 6 per group). Positive and negative control samples are shown. Original magnification, ×300. (H) Lamina propria cells were isolated from either TNBS-treated WT or IRF4^–/– mice (n = 6 per group) and stained for CD3 and annexin V. Lamina propria cells from IRF4^–/– mice showed more annexin V and CD3 double-positive cells than those from WT mice (15% versus 3%). No such differences were detected in spleen cells (8% versus 11%).