STAT4 Is Required for IFN-[beta]-Induced MCP-1 mRNA Expression in Murine Mast Cells

Background: Mast cells are immunocompetent cells that are found in almost all tissues and function as sentinels of immune responses. Recently, it has been shown that mast cells play significant roles in innate immune responses. However, it is still largely unknown whether signal transducers and activators of transcription 4 (STAT4), one of the STAT proteins under type I IFN signaling, is involved in type I IFN-mediated gene expression in mast cells. Methods: We investigated the role of STAT4 in IFN-β-induced gene expression in mast cells by using STAT4-deficient (STAT4-/-) bone marrow-derived mast cells (BMMCs). Results: STAT4 was expressed in BMMCs and activated in response to IFN-β but not to IL-12 or IL-23. The development of BMMCs as well as IgE-induced degranulation of BMMCs was normal in STAT4-/- mice. On the other hand, while IFN-β-induced mRNA expression of interferon-induced protein with tetratricopeptide repeats 1 (IFIT-1), protein kinase interferon-inducible double stranded RNA dependent (PKR), and myxovirus resistance 1 (Mx1) was similar between STAT4-/- BMMCs and wild-type (WT) BMMCs, IFN-β-induced MCP-1 mRNA expression was severely diminished in STAT4-/- BMMCs as compared with WT BMMCs. Conclusions: STAT4 plays an essential role in IFN-β-induced MCP-1 mRNA expression in mast cells. [PUBLICATION ABSTRACT]