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Lewis-antigen-containing ICAM-2/3 on Jurkat leukemia cells interact with DC-SIGN to regulate DC functions
Xin Jin1, Qingpan Bu2, Yingying Zou1
1Key Laboratory of Molecular Epigenetics of the Ministry of Education (MOE), Northeast Normal University, 5268 Renmin Street, Changchun, Jilin, 130024, People's Republic of China.
Abstract:
Dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN) is an important C-type lectin and plays a critical role in the recognition of pathogens and self-antigens. It has recently been shown that DC-SIGN directly interacts with acute T lymphoblastic leukemia cells. However, the mechanism regulating DC-SIGN-dependent DC association as well as related functions is still elusive. Here we showed that DC-SIGN preferentially bound to a set of malignant T lymphocytes, including Jurkat, CCRF-HSB2 and CCRF-CEM. ICAM-2/3 on Jurkat cells appeared to be the responsible ligands and the block of ICAM-2/3 dramatically impaired DC-SIGN association. We also found that ICAM-2/3 bear a considerable amount of Lewis X, Lewis Y and Lewis A residues, which are important for DC-SIGN recognition. Furthermore, transcriptome analysis revealed an upregulation of fucosyltransferase 4 (FUT4) in Jurkat cells and downregulating FUT4 limited DC-SIGN binding, indicating a previously unappreciated role of FUT4 in the control of Lewis antigens on malignant T lymphocytes. In addition, the presence of Jurkat cells impaired DC maturation and the block of DC-SIGN improved Jurkat cell-mediated effects on DC function and T cell differentiation. Together, we provide evidence that DC-SIGN orients DC association with acute T lymphoblastic leukemia cells and orchestrates DC functions.
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