期刊
IMMUNOLOGY LETTERS
卷 136, 期 1, 页码 21-28出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.imlet.2010.11.007
关键词
Interleukin-27; Tr1 cells; STATs; Naive; CD4(+) T cells
类别
资金
- National Key Basic Research Program of China (973) [2007CB512404]
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-gamma, but had no effect on IL-2, TNF-alpha 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-gamma. 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. (C) 2010 Elsevier B.V. All rights reserved.
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