DJ-1 protein regulates CD3+ T cell migration via overexpression of CXCR4 receptor.

DJ-1-a multifunctional protein responding to oxidative stress-is a possible regulator of the inflammatory response that plays an important role in atherosclerosis. Stromal cell-derived factor (SDF)-1 and its receptor, chemokine receptor type 4 (CXCR4), have been implicated in the recruitment of inflammatory cells during atherosclerosis. Here we investigated the hypothesis that DJ-1 protein might participate in CD3+ T cell functions in response to SDF-1 and contribute to the pathogenesis of atherosclerosis. SDF-1 stimulated migration in mouse CD3+ T cells in a dose-dependent manner. SDF-1 also elevated the phosphorylation level of extracellular-regulated kinase (ERK) 1/2 in CD3+ T cells. These SDF-1-induced responses were greater in CD3+ T cells from DJ-1 gene knockout (DJ-1(-/-)) mice than in those from wild type (DJ-1(+/+)) mice and were abolished by treatment with WZ811 and PD98059, inhibitors of CXCR4 and ERK1/2, respectively. Flow cytometry revealed that expression of the CXCR4 receptor was greater in CD3+ T cells from DJ-1(-/-) mice than in those from the controls. Moreover, expression of the CD3 protein was observed in the neointimal plaque from carotid artery-ligated mice and was stronger in DJ-1(-/-) mice compared with controls. The CD3+ T cell subsets, Th1 and Th17, showed increased production of interferon-γ and interleukin-17 in DJ-1(-/-) compared with DJ-1(+/+) mice. DJ-1 protein is involved in the SDF-1-induced CD3+ T cell migration via overexpression of the CXCR4 receptor, and that DJ-1 acts as an inhibitory regulator in vascular remodeling such as neointima formation. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Citation

Seung Hyo Jung, Kyung Jong Won, Kang Pa Lee, Dong Hyun Lee, Suyeol Yu, Dong-Youb Lee, Eun-Hye Seo, Hyun Kang, Eun-Seok Park, Hyun-Joong Kim, Seung Hyun Lee, Bokyung Kim. DJ-1 protein regulates CD3+ T cell migration via overexpression of CXCR4 receptor. Atherosclerosis. 2014 Aug;235(2):503-9

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PMID: 24953490

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