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.
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.
Pot
Caroline
C
Center for Neurologic Diseases, Brigham and Women's Hospital, Boston, MA 02115, USA.
Jin
Hulin
H
Awasthi
Amit
A
Liu
Sue Min
SM
Lai
Chen-Yen
CY
Madan
Rajat
R
Sharpe
Arlene H
AH
Karp
Christopher L
CL
Miaw
Shi-Chuen
SC
Ho
I-Cheng
IC
Kuchroo
Vijay K
VK
D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte / Q000235:genetics / Q000502:physiology*; D002454:Cell Differentiation; D060889:Inducible T-Cell Co-Stimulator Protein; D016753:Interleukin-10 / Q000096:biosynthesis; D007378:Interleukins / Q000235:genetics / Q000276:immunology* / Q000502:physiology*; D051379:Mice; D051257:Proto-Oncogene Proteins c-maf / Q000235:genetics / Q000502:physiology*; D050378:T-Lymphocytes, Regulatory / Q000166:cytology* / Q000378:metabolism; D015533:Transcriptional Activation; D000098546:Interleukin-21
D000945:Antigens, Differentiation, T-Lymphocyte; C556694:Icos protein, mouse; C486767:Il27 protein, mouse; D060889:Inducible T-Cell Co-Stimulator Protein; D007378:Interleukins; C495608:Maf protein, mouse; D051257:Proto-Oncogene Proteins c-maf; D016753:Interleukin-10; D000098546:Interleukin-21