A novel IL-25 signaling pathway through STAT5.
J Immunol
; 194(9): 4528-34, 2015 May 01.
Article
en En
| MEDLINE
| ID: mdl-25821217
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.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Transducción de Señal
/
Interleucinas
/
Factor de Transcripción STAT5
Tipo de estudio:
Prognostic_studies
Límite:
Animals
/
Humans
Idioma:
En
Revista:
J Immunol
Año:
2015
Tipo del documento:
Article