Archivum Immunologiae et Therapiae Experimentalis

, Volume 57, Issue 5, pp 369–376

IRF4 selectively controls cytokine gene expression in chronic intestinal inflammation

  • Jonas Mudter
  • Jingling Yu
  • Lioubov Amoussina
  • Benno Weigmann
  • Arthur Hoffman
  • Katrin Rücknagel
  • Peter R. Galle
  • Markus F. Neurath
Open Access
Original Article

DOI: 10.1007/s00005-009-0046-5

Cite this article as:
Mudter, J., Yu, J., Amoussina, L. et al. Arch. Immunol. Ther. Exp. (2009) 57: 369. doi:10.1007/s00005-009-0046-5

Abstract

The authors previously showed that interferon regulatory factor (IRF)4 knockout mice are protected from experimental oxazolone and TNBS colitis. Here the effect of IRF4 on the expression of pro- and anti-inflammatory cytokines in TNBS colitis and long-term CD45RBhigh transfer colitis is examined. In TNBS colitis, no differences were found in interleukin (IL)-18 and tumor necrosis factor (TNF)-α expression between IRF4 knockout and wild-type mice. However, significant differences were detected in IL-6 and IL-17 production. Upon treatment with hyper-IL-6, IRF4–/– mice lost their protective properties towards TNBS application. Hyper-IL-6 application induced IL-6 mRNA, but not IL-17 mRNA expression, suggesting that IL-6 deficiency is not primarily responsible for the lack of IL-17 production. T-bet and GATA-3 mRNA expressions were not affected upon IL-6 application. In transfer colitis, colonic cytokine mRNA analysis revealed a reduced production of IL-6 in IRF4–/– reconstituted mice in the long-term course. In contrast, several other cytokines did not differ between the two groups (e.g. TNF-α and IL-10). Measurement of supernatants from splenic mononuclear cells revealed a significant difference in IL-6 and IL-17 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 inflammation.

Keywords

IRF4 T cells interferon regulatory factor IL-6 IL-17 

Copyright information

© L. Hirszfeld Institute of Immunology and Experimental Therapy, Wroclaw, Poland 2009

Authors and Affiliations

  • Jonas Mudter
    • 1
    • 2
    • 3
  • Jingling Yu
    • 2
  • Lioubov Amoussina
    • 2
  • Benno Weigmann
    • 2
  • Arthur Hoffman
    • 3
  • Katrin Rücknagel
    • 3
  • Peter R. Galle
    • 3
  • Markus F. Neurath
    • 1
    • 2
    • 3
  1. 1.Medizinische Klinik 1Universität Erlangen-NürnbergErlangenGermany
  2. 2.Institute for Molecular MedicineUniversity of MainzMainzGermany
  3. 3.1st Medical ClinicUniversity of MainzMainzGermany

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