Tyk2 is essential for IFN-alpha-induced gene expression in mast cells.
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-alpha, they expressed mRNA for IFN-gamma-inducible protein 10 (IP-10) and monocyte chemoattractant protein-5 (MCP-5). Interestingly, IFN-alpha-induced expression of IP-10 and MCP-5 was severely decreased in Tyk2(-/-) BMMCs. In addition, IFN-alpha-induced Stat1 phosphorylation was decreased in Tyk2(-/-) BMMCs. On the other hand, IFN-alpha-induced Stat1 phosphorylation and IP-10 and MCP-5 expression were normal in Tyk2(-/-) fibroblasts. These results indicate that IFN-alpha induces the expression of TNF-alpha and the chemokines IP-10 and MCP-5 in mast cells and thatTyk2 plays a nonredundant role in IFN-alpha signaling in mast cells.
Mori
Yumiko
Y
Department of Internal Medicine II, Chiba University School of Medicine, Chiba, Japan.
Hirose
Koichi
K
Suzuki
Kotaro
K
Nakajima
Hiroshi
H
Seto
Yohei
Y
Ikeda
Kei
K
Shimoda
Kazuya
K
Nakayama
Kei-ichi
K
Saito
Yasushi
Y
Iwamoto
Itsuo
I
D000818:Animals; D002478:Cells, Cultured; D054357:Chemokine CXCL10; D019743:Chemokines, CXC / Q000096:biosynthesis; D004268:DNA-Binding Proteins / Q000187:drug effects / Q000378:metabolism; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000276:immunology*; D016898:Interferon-alpha / Q000276:immunology / Q000494:pharmacology*; D008407:Mast Cells / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D018945:Monocyte Chemoattractant Proteins / Q000096:biosynthesis; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050794:STAT1 Transcription Factor; D015398:Signal Transduction / Q000276:immunology*; D053634:TYK2 Kinase; D015534:Trans-Activators / Q000187:drug effects / Q000378:metabolism
C491224:Ccl12 protein, mouse; D054357:Chemokine CXCL10; D019743:Chemokines, CXC; D004268:DNA-Binding Proteins; D016898:Interferon-alpha; D018945:Monocyte Chemoattractant Proteins; D050794:STAT1 Transcription Factor; C494080:Stat1 protein, mouse; D015534:Trans-Activators; D011505:Protein-Tyrosine Kinases; D053634:TYK2 Kinase; C499356:Tyk2 protein, mouse