IL-27 induces the differentiation of Tr1-like cells from human naive CD4+ T cells via the phosphorylation of STAT1 and STAT3.
IL-27, a member of IL-6/IL-12 cytokine family, is mainly produced by activated antigen presenting cells (APC). It has been demonstrated that IL-27 has the pro- and anti-inflammatory properties during immune responses. However, the signaling pathways that contribute to the cytokine generation are still unclear in humans. In the present study, we showed that IL-27 induced IL-10 and IFN-γ, but had no effect on IL-2, TNF-α and IL-4 production from human umbilical cord blood mononuclear cells (CBMCs). For purified naive CD4(+) T cells, IL-27 elicited the differentiation of Tr1-like cells with expression of IL-10 and IFN-γ. Importantly, this induction was dependent on the signal transducer and activator of transcription (STAT) 1 and 3 factors. In addition, all of the phosphorylated STAT3 positive cells were also positive for phosphorylated STAT1, both of which could be inhibited by a JAK2/STAT inhibitor, AG490. However, there was no phosphorylation of STAT4, STAT5 and STAT6 in IL-27-stimulating conditions. Moreover, the biological function of IL-10 that was induced by IL-27 mainly enhanced the expression of CD16 without influencing CD14 expression on human monocytes. These data identify the function of IL-27 on the differentiation of human naive CD4(+) T cells and demonstrate that the STATs signaling pathways may play an important role in mediating immune responses in humans.
Department of Immunology, Zhongshan School of Medicine, Key Laboratory of Tropical Disease Control Research of Ministry of Education, Sun Yat-sen University, Guangzhou, PR China.
Hui
H
Wang
Rui
R
Meng
Zitao
Z
Li
Binyan
B
Yang
Yun
Y
Liu
Fengyu
F
Huang
Jianping
J
Zhang
Hui
H
Chen
Changyou
C
Wu
D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D002454:Cell Differentiation; D002478:Cells, Cultured; D006801:Humans; D007231:Infant, Newborn; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis; D007378:Interleukins / Q000276:immunology*; D010766:Phosphorylation; D050794:STAT1 Transcription Factor / Q000276:immunology* / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000276:immunology* / Q000378:metabolism; D015398:Signal Transduction
C508609:IL10 protein, human; D007378:Interleukins; C464565:MYDGF protein, human; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D016753:Interleukin-10; D007371:Interferon-gamma