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 [Go to this article.]

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%).