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. 2001 Apr 1;166(7):4446-55.
doi: 10.4049/jimmunol.166.7.4446.

Inducible expression of Stat4 in dendritic cells and macrophages and its critical role in innate and adaptive immune responses

T Fukao  1 , D M Frucht, G Yap, M Gadina, J J O'Shea, S Koyasu
Affiliations

Inducible expression of Stat4 in dendritic cells and macrophages and its critical role in innate and adaptive immune responses

T Fukao et al. J Immunol. .

Abstract

Autocrine activation of APC by IL-12 has recently been revealed; we demonstrate here that inducible expression of Stat4 in APC is central to this process. Stat4 is induced in dendritic cells (DC) in a maturation-dependent manner and in macrophages in an activation-dependent manner. Stat4 levels directly correlate with IL-12-dependent IFN-gamma production by APC as well as IFN-gamma production by DC during Ag presentation. The Th2 cytokines IL-4 and IL-10 suppress Stat4 induction in DC and macrophages when present during maturation and activation, respectively, diminishing IFN-gamma production. In contrast, IL-4 has no effect on Stat4 levels in mature DC and actually augments IFN-gamma production by DC during Ag presentation, indicating that IL-4 acts differently in a spatiotemporal manner. The functional importance of Stat4 is evident in Stat4(-/-) DC and macrophages, which fail to produce IFN-gamma. Furthermore, Stat4(-/-) macrophages are defective in NO production in response to IL-12 and are susceptible to TOXOPLASMA: Autocrine IL-12 signaling is required for high-level IFN-gamma production by APC at critical stages in both innate and adaptive immunity, and the control of Stat4 expression is likely an important regulator of this process.

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