| First Author | Wu L | Year | 2015 |
| Journal | J Immunol | Volume | 194 |
| Issue | 9 | Pages | 4528-34 |
| PubMed ID | 25821217 | Mgi Jnum | J:329797 |
| Mgi Id | MGI:6871841 | Doi | 10.4049/jimmunol.1402760 |
| Citation | Wu L, et al. (2015) A novel IL-25 signaling pathway through STAT5. J Immunol 194(9):4528-34 |
| abstractText | 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. |
