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PI 3K‐Akt pathway enhances the differentiation of interleukin‐27‐induced type 1 regulatory T cells
Author(s) -
Nadya Niken Adiba,
Tezuka Hiroyuki,
Ohteki Toshiaki,
Matsuda Satoshi,
Azuma Miyuki,
Nagai Shigenori
Publication year - 2017
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/imm.12789
Subject(s) - pi , microbiology and biotechnology , protein kinase b , chemistry , interleukin 4 , pi3k/akt/mtor pathway , biology , signal transduction , immunology , cytokine , biochemistry
Summary 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 ( PI 3K) –Akt axis contributes to the differentiation of helper T‐cell subsets, the role of the PI 3K pathway on Tr1 cell differentiation remains to be elucidated. Here, we demonstrate that suppression of the PI 3K‐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 PI 3K pathway enhances IL ‐10 expression by IL ‐27–Tr1 cells through up‐regulation of IL ‐21 receptors.