期刊
FRONTIERS IN IMMUNOLOGY
卷 9, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2018.01263
关键词
CCR2; Stat3; forkhead box O1; sphingosine-1-phosphate receptor 1; thymic egress
类别
资金
- National Natural Sciences Foundation of China [31330025, 31000393, 81621063]
- Natural Basic Research Program of China [2015CB943201, 2011CB946100]
- Beijing Natural Science Foundation [7172114]
- 111 Project of China [B07001]
The signal mediated by sphingosine-1-phosphate receptor 1 (S1P1) is essential but seemingly insufficient for thymic export of newly generated T cells. Here, we reported the identification of CCR2 as an additional regulator of this process. CCR2 showed a markedly increased expression in the most mature subset of single-positive (SP) thymocytes. Its deficiency led to a reduction of recent thymic emigrants in the periphery and a simultaneous accumulation of mature SP cells in the thymus. The CCR2 signaling promoted thymic emigration primarily through modulating the chemotactic responses to S1P1 engagement. On the one hand, the chemokinesis induced by CCR2 activation endowed thymocytes with enhanced capacity to respond to S1P-induced migration. On the other hand, CCR2 signaling through Stat3 augmented forkhead box O1 activity, leading to increased expression of S1P1 . Taken together, the present study highlights a unique and novel function of CCR2 signaling in the regulation of thymic egress.
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