期刊
JOURNAL OF IMMUNOLOGY
卷 194, 期 9, 页码 4528-4534出版社
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.1402760
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资金
- National Institute of Neurological Disorders and Stroke/National Institutes of Health [R01-NS071996]
- National Heart, Lung, and Blood Institute/National Institute of Neurological Disorders and Stroke/National Institutes of Health [P01-HL103453]
- National Institute of General Medical Sciences [T32 GM007250]
- National Institute of Allergy and Infectious Diseases [T32 AI 89474-1]
IL-25 is a member of the IL-17 family of cytokines that promotes Th2 cell-mediated inflammatory responses. IL-25 signals through a heterodimeric receptor (IL-25R) composed of IL-17RA and IL-17RB, which recruits the adaptor molecule Act1 for downstream signaling. Although the role of IL-25 in potentiating type 2 inflammation is well characterized by its ability to activate the epithelium as well as T cells, the components of its signaling cascade remain largely unknown. In this study, we found that IL-25 can directly activate STAT5 independently of Act1. Furthermore, conditional STAT5 deletion in T cells or epithelial cells led to a defective IL-25-initiated Th2 polarization as well as defective IL-25 enhancement of Th2 responses. Finally, we found that STAT5 is recruited to the IL-25R in a ligand-dependent manner through unique tyrosine residues on IL-17RB. Together, these findings reveal a novel Act1-independent IL-25 signaling pathway through STAT5 activation.
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