PI3K-Akt pathway enhances the differentiation of interleukin-27-induced type 1 regulatory T cells.
Immunology
; 152(3): 507-516, 2017 11.
Article
in En
| MEDLINE
| ID: mdl-28685820
ABSTRACT
Interleukin 27 (IL-27) has been identified as a potent cytokine in the differentiation of type 1 regulatory T (Tr1) cells through interactions with several key elements, including transcription factors such as aryl hydrocarbon receptor and IL-21. Autocrine production of IL-21 is known to be important for maintaining IL-10 expression by Tr1 cells. Although previous studies have shown that the phosphoinositide 3-kinase (PI3K) -Akt axis contributes to the differentiation of helper T-cell subsets, the role of the PI3K pathway on Tr1 cell differentiation remains to be elucidated. Here, we demonstrate that suppression of the PI3K-Akt pathway results in impairment of IL-27-induced Tr1 (IL-27-Tr1) cell differentiation in vitro and in vivo. Furthermore, this suppression down-regulates IL-21 receptor expression by Tr1 cells, followed by suppression of IL-10 expression by IL-27-Tr1 cells. These results suggest that the PI3K pathway enhances IL-10 expression by IL-27-Tr1 cells through up-regulation of IL-21 receptors.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Signal Transduction
/
Cell Differentiation
/
T-Lymphocytes, Regulatory
/
Proto-Oncogene Proteins c-akt
/
Phosphatidylinositol 3-Kinase
/
Interleukin-27
Type of study:
Prognostic_studies
Limits:
Animals
Language:
En
Journal:
Immunology
Year:
2017
Type:
Article
Affiliation country:
Japan