%0 Journal Article
%T A Crucial Role of CXCL14 for Promoting Regulatory T Cells Activation in Stroke
%A Chen-Huan Lin
%A Chia-Hung Hsieh
%A Chung Y. Hsu
%A Hsu-Tung Lee
%A Huey-Kang Sytwu
%A Shih-Ping Liu
%A Sophie Wei Lee
%A Woei-Cherng Shyu
%J Theranostics
%D 2017
%I Ivyspring International Publisher
%R 10.7150/thno.17558
%X Inflammatory processes have a detrimental role in the pathophysiology of ischemic stroke. However, little is known about the endogenous anti-inflammatory mechanisms in ischemic brain. Here, we identify CXCL14 as a critical mediator of these mechanisms. CXCL14 levels were upregulated in the ischemic brains of humans and rodents. Moreover, hypoxia inducible factor-1¦Á (HIF-1¦Á) drives hypoxia- or cerebral ischemia (CI)-dependent CXCL14 expression via directly binding to the CXCL14 promoter. Depletion of CXCL14 inhibited the accumulation of immature dendritic cells (iDC) or regulatory T cells (Treg) and increased the infarct volume, whereas the supplementation of CXCL14 had the opposite effects. CXCL14 promoted the adhesion, migration, and homing of circulating CD11c+ iDC to the ischemic tissue via the upregulation of the cellular prion protein (PrPC), PECAM-1, and MMPs. The accumulation of Treg in ischemic areas of the brain was mediated through a cooperative effect of CXCL14 and iDC-secreted IL-2-induced Treg differentiation. Interestingly, CXCL14 largely promoted IL-2-induced Treg differentiation. These findings indicate that CXCL14 is a critical immunomodulator involved in the stroke-induced inflammatory reaction. Passive CXCL14 supplementation provides a tractable path for clinical translation in the improvement of stroke-induced neuroinflammation.
%K CXC chemokine 14 (CXCL14)
%K regulatory T cells (Treg)
%K immature dendritic cells (iDC)
%K cerebral ischemia
%K hypoxia inducible factor 1¦Á (HIF-1¦Á).
%U http://www.thno.org/v07p0855.htm