Tyk2 Is Essential for IFN-α-Induced Gene Expression in Mast Cells

Abstract

Mast cells are recognized not only as the major effector cells of type I hypersensitivity reactions but also as an important player of innate immune response against bacterial infection. Type I IFNs are also involved in the response against bacterial infection. However, the role of type I IFNs and their associated Janus kinase Tyk2 in mast cell functions remains to be determined. In this study, we addressed this issue using Tyk2-deficient (Tyk2^–/–) bone marrow-derived mast cells (BMMCs). When BMMCs from wild-type (WT) mice were stimulated with IFN-α, they expressed mRNA for IFN-γ-inducible protein 10 (IP-10) and monocyte chemoattractant protein-5 (MCP-5). Interestingly, IFN-α-induced expression of IP-10 and MCP-5 was severely decreased in Tyk2^–/– BMMCs. In addition, IFN-α-induced Stat1 phosphorylation was decreased in Tyk2^–/– BMMCs. On the other hand, IFN-α-induced Stat1 phosphorylation and IP-10 and MCP-5 expression were normal in Tyk2^–/– fibroblasts. These results indicate that IFN-α induces the expression of TNF-α and the chemokines IP-10 and MCP-5 in mast cells and thatTyk2 plays a nonredundant role in IFN-α signaling in mast cells.