Leukocyte-specific protein 1 regulates T-cell migration in rheumatoid arthritis
2015
Hwang, Seong-hye | Jung, Seung-Hyun | Lee, Saseong | Choi, Susanna | Yoo, Seung-Ah | Park, Ji-Hwan | Hwang, Daehee | Shim, Seung Cheol | Sabbagh, Laurent | Kim, Ki-Jo | Pak, Sŏng-hwan | Cho, Chul-Soo | Kim, Bong-Sung | Leng, Lin | Montgomery, Ruth R. | Bucala, Richard | Chung, Yeun-Jun | Kim, Wan-Uk
Significance We screened rheumatoid arthritis (RA)-associated copy number variations (CNVs) across the whole genome and identified significant deletion variants encompassing leukocyte-specific protein 1 (LSP1) gene. Functional assays revealed that LSP1, induced by T-cell receptor activation, negatively regulates T-cell migration. Loss of Lsp1 promotes T-cell migration into antigen-instilled tissues and draining lymph nodes in mice with T-cell–dependent chronic inflammation. Moreover, patients with RA show diminished expression of LSP1 in peripheral T cells with increased migratory capacity. To our knowledge, our work is the first to demonstrate how CNVs result in immune dysfunction and a disease phenotype, highlighting the importance of LSP1 CNVs and LSP1 insufficiency in the pathogenesis of RA.
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