Open AccessInterleukin‐25 initiates Th2 differentiation of human CD4 + T cells and influences expression of its own receptor
Author(s) -
Bredo Graeme,
Storie Jessica,
Shrestha Palikhe Nami,
Davidson Courtney,
Adams Alexis,
Vliagoftis Harissios,
Cameron Lisa
Publication year - 2015
Publication title -
immunity, inflammation and disease
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.918
H-Index - 18
ISSN - 2050-4527
DOI - 10.1002/iid3.87
Subject(s) - gata3 , cellular differentiation , receptor , interleukin 4 , biology , il 2 receptor , cytokine , microbiology and biotechnology , flow cytometry , downregulation and upregulation , chemistry , immunology , t cell , immune system , transcription factor , gene , biochemistry
Human CRTh2 + Th2 cells express IL‐25 receptor (IL‐25R) and IL‐25 has been shown to potentiate production of Th2 cytokines. However, regulation of IL‐25R and whether it participates in Th2 differentiation of human cells have not been examined. We sought to characterize IL‐25R expression on CD4 + T cells and determine whether IL‐25 plays a role in Th2 differentiation. Naïve human CD4 + T cells were activated in the presence of IL‐25, IL‐4 (Th2 conditions) or both cytokines to assess their relative influence on Th2 differentiation. For experiments with differentiated Th2 cells, CRTh2‐expressing cells were isolated from differentiating cultures. IL‐25R, GATA3, CRTh2 and Th2 cytokine expression were assessed by flow cytometry, qRT‐PCR and ELISA. Expression of surface IL‐25R was induced early during Th2 differentiation (2 days). Addition of IL‐25 to naïve CD4 + T cells revealed that it induces expression of its own receptor, more strongly than IL‐4. IL‐25 also increased the proportions of IL‐4‐, GATA3‐ and CRTh2‐expressing cells and expression of IL‐5 and IL‐13. Activation of differentiated CRTh2 + Th2 cells through the TCR or by CRTh2 agonist increased surface expression of IL‐25R, though re‐expression of CRTh2 following TCR downregulation was impeded by IL‐25. These data suggest that IL‐25 may play various roles in Th2 mediated immunity. We establish here it regulates expression of its own receptor and can initiate Th2 differentiation, though not as strongly as IL‐4.