Cutting edge: IL-27 induces the transcription factor c-Maf, cytokine IL-21, and the costimulatory receptor ICOS that coordinately act together to promote differentiation of IL-10-producing Tr1 cells
Journal
Journal of immunology (Baltimore, Md. : 1950)
Journal Volume
183
Journal Issue
2
Pages
797
Date Issued
2009-07-15
Author(s)
Pot, Caroline
Jin, Hulin
Awasthi, Amit
Liu, Sue Min
Lai, Chen-Yen
Madan, Rajat
Sharpe, Arlene H
Karp, Christopher L
Ho, I-Cheng
Kuchroo, Vijay K
Abstract
IL-27 has recently been identified as a differentiation factor for the generation of IL-10-producing regulatory type 1 (Tr1) T cells. However, how IL-27 induces the expansion of Tr1 cells has not been elucidated. In this study we demonstrate that IL-27 drives the expansion and differentiation of IL-10-producing murine Tr1 cells by inducing three key elements: the transcription factor c-Maf, the cytokine IL-21, and the costimulatory receptor ICOS. IL-27-driven c-Maf expression transactivates IL-21 production, which acts as an autocrine growth factor for the expansion and/or maintenance of IL-27-induced Tr1 cells. ICOS further promotes IL-27-driven Tr1 cells. Each of those elements is essential, because loss of c-Maf, IL-21-signaling, or ICOS decreases the frequency of IL-27-induced differentiation of IL-10-producing Tr1 cells.
Publisher
AMER ASSOC IMMUNOLOGISTS
Type
journal article