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    Proc Natl Acad Sci U S A. 2002 Sep 3;99(18):11808-12. Epub 2002 Aug 20.

    Dysregulated T helper cell differentiation in the absence of interferon regulatory factor 4.

    Lohoff M, Mittrücker HW, Prechtl S, Bischof S, Sommer F, Kock S, Ferrick DA, Duncan GS, Gessner A, Mak TW.

    Institut für Medizinische Mikrobiologie, Pilgrimstein 2, 35037 Marburg, Germany.

    Certain IFN regulatory factor (IRF) transcription factors indirectly influence T helper (Th) cell differentiation by regulating the production of IL-12. Here, we show that IRF4 directly regulates Th cell differentiation in vitro and in vivo during murine leishmaniasis. In the absence of IRF4, IL-12-induced Th1 cell differentiation was compromised, while IL-4 failed to induce Th2 cell differentiation. Instead, IL-4 tended to induce Th1 cells, defined by production of IFN-gamma and TNF. Although early IL-4 signaling was normal in IRF4(-/-) Th cells, the protein GATA-3, a transcription factor critical for Th2 development, was not up-regulated following IL-4 treatment. Retroviral overexpression of GATA-3 rescued Th2 differentiation. Therefore, IRF4 deficiency manifests itself as severely dysregulated Th cell differentiation.

    PMID: 12189207 [PubMed - indexed for MEDLINE]

    PMCID: 129350

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