Dysregulated T helper cell differentiation in the absence of interferon regulatory factor 4
M Lohoff, HW Mittrücker, S Prechtl… - Proceedings of the …, 2002 - National Acad Sciences
M Lohoff, HW Mittrücker, S Prechtl, S Bischof, F Sommer, S Kock, DA Ferrick, GS Duncan…
Proceedings of the National Academy of Sciences, 2002•National Acad SciencesCertain 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-γ and TNF. Although early IL-4 signaling was normal in IRF4−/− Th cells …
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-γ and TNF. Although early IL-4 signaling was normal in IRF4−/− Th cells …
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-γ 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.
National Acad Sciences