| Content Provider |
World Health Organization (WHO)-Global Index Medicus |
| Author |
Ouyang, Wenjun Yin, Weiguo Bunting, Kevin D. Wu, Ling Zepp, Jarod A. Qian, Wen Li, Xiaoxia Martin, Bradley N. Aronica, Mark Erzurum, Serpil |
| Description |
Author Affiliation: Wu L ( Department of Immunology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195); Zepp JA ( Department of Immunology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195); Qian W ( Department of Immunology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195); Martin BN ( Department of Immunology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195); Ouyang W ( Department of Immunology, Genentech, South San Francisco, CA 94080); Yin W ( Department of Immunology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195); Bunting KD ( Aflac Cancer and Blood Disorders Center of Children's Healthcare of Atlanta, Atlanta, GA 30329); Aronica M ( Department of Pathobiology, Lerner Research Institute, The Cleveland Clinic Foundation, Cleveland, OH 44195.); Erzurum S ( Department of Pathobiology, Lerner Research Institute, The Cleveland Clinic Foundation, Cleveland, OH 44195.); Li X ( Department of Immunology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195) |
| Abstract |
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. |
| ISSN |
00221767 |
| e-ISSN |
15506606 |
| DOI |
10.4049/jimmunol.1402760 |
| Journal |
The Journal of Immunology |
| Issue Number |
9 |
| Volume Number |
194 |
| Language |
English |
| Publisher |
The American Association of Immunologists |
| Publisher Date |
2015-05-01 |
| Publisher Place |
United States |
| Access Restriction |
Open |
| Subject Keyword |
Interleukins Metabolism Stat5 Transcription Factor Signal Transduction Animals Cell Line Connexin 43 Cytokines Epithelial Cells Drug Effects Ligands Mice Mice, Transgenic Models, Biological Peptide Fragments Protein Binding Receptors, Interleukin Receptors, Interleukin-17 Th2 Cells Immunology Research Support, N.i.h., Extramural Discipline Immunology |
| Content Type |
Text |
| Resource Type |
Article |
| Subject |
Immunology and Allergy Immunology |
