A Novel IL-25 Signaling Pathway through STAT5

作者：Wu Ling; Zepp Jarod A; Qian Wen; Martin Bradley N; Ouyang Wenjun; Yin Weiguo; Bunting Kevin D; Aronica Mark; Erzurum Serpil; Li Xiaoxia^*

来源：The Journal of Immunology, 2015, 194(9): 4528-4534.

DOI：10.4049/jimmunol.1402760

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.

• 出版日期2015-5-1