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

作者：Jung Seung Hyo; Won Kyung Jong; Lee Kang Pa; Lee Dong Hyun; Yu Suyeol; Lee Dong Youb; Seo Eun Hye; Kang Hyun; Park Eun Seok; Kim Hyun Joong; Lee Seung Hyun; Kim Bokyung^*

来源：Atherosclerosis, 2014, 235(2): 503-509.

DOI：10.1016/j.atherosclerosis.2014.05.955

• CD3+T cell migration
• DJ-1
• Stromal cell-derived factor-1
• Atherosclerotic plaque
• CXCR4 receptor

Objective: DJ-1da 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. Methods and results: 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-gamma and interleukin-17 in DJ-1(-/-) compared with DJ-1(+/+) mice. Conclusion: 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 neo-intima formation.

• 出版日期2014-8