IRF4 selectively controls cytokine gene expression

Authors: Jonas Mudter Jingling Yu Lioubov Amoussina Benno Weigmann Arthur Hoffman Katrin Rücknagel Peter R Galle Markus F Neurath

Publish Date: 2009/08/20

Volume: 57, Issue: 5, Pages: 369-376

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Abstract

The authors previously showed that interferon regulatory factor IRF4 knockout mice are protected from experimental oxazolone and TNBS colitis Here the effect of IRF4 on the expression of pro and antiinflammatory cytokines in TNBS colitis and longterm CD45RBhigh transfer colitis is examined In TNBS colitis no differences were found in interleukin IL18 and tumor necrosis factor TNFα expression between IRF4 knockout and wildtype mice However significant differences were detected in IL6 and IL17 production Upon treatment with hyperIL6 IRF4–/– mice lost their protective properties towards TNBS application HyperIL6 application induced IL6 mRNA but not IL17 mRNA expression suggesting that IL6 deficiency is not primarily responsible for the lack of IL17 production Tbet and GATA3 mRNA expressions were not affected upon IL6 application In transfer colitis colonic cytokine mRNA analysis revealed a reduced production of IL6 in IRF4–/– reconstituted mice in the longterm course In contrast several other cytokines did not differ between the two groups eg TNFα and IL10 Measurement of supernatants from splenic mononuclear cells revealed a significant difference in IL6 and IL17 production between the two groups These findings suggest that IRF4 selectively regulates cytokine gene expression in chronic inflammation IRF4 therefore emerges as an attractive target for the therapy of chronic intestinal inflammation Blocking IRF4 might be an interesting option to modulate inflammation in the advanced state of inflammationThis article is published under an open access license Please check the Copyright Information section for details of this license and what reuse is permitted If your intended use exceeds what is permitted by the license or if you are unable to locate the licence and reuse information please contact the Rights and Permissions team

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