The Leukocyte Activation Receptor CD69 Controls T Cell Differentiation through Its Interaction with Galectin-1

被引:89
作者
de la Fuente, Hortensia [1 ,2 ]
Cruz-Adalia, Aranzazu [1 ]
Martinez del Hoyo, Gloria [2 ]
Cibrian-Vera, Danay [1 ]
Bonay, Pedro [3 ]
Perez-Hernandez, Daniel [4 ]
Vazquez, Jesus [4 ]
Navarro, Pilar [5 ]
Gutierrez-Gallego, Ricardo [6 ,7 ]
Ramirez-Huesca, Marta [2 ]
Martin, Pilar [2 ]
Sanchez-Madrid, Francisco [1 ,2 ]
机构
[1] Univ Autonoma Madrid, Hosp Princesa, Serv Inmunol, Inst Invest Sanitaria Princesa, Madrid, Spain
[2] Ctr Nacl Invest Cardiovasc Carlos III, Dept Vasc Biol & Inflammat, Madrid, Spain
[3] Univ Autonoma Madrid, CSIC, Ctr Biol Mol Severo Ochoa, Madrid, Spain
[4] Ctr Nacl Invest Cardiovasc Carlos III, Lab Cardiovasc Proteom, Madrid, Spain
[5] Hosp Mar Res Inst, Canc Res Program, Barcelona, Spain
[6] Hosp Mar Res Inst, Neurosci Res Program, Barcelona, Spain
[7] Pompeu Fabra Univ, Barcelona, Spain
关键词
GROWTH-FACTOR-BETA; DENDRITIC CELLS; TOLEROGENIC SIGNALS; INDUCER MOLECULE; MISSING-SELF; CUTTING EDGE; ANTIGEN; BINDING; LYMPHOCYTES; EXPRESSION;
D O I
10.1128/MCB.00348-14
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
070307 [化学生物学]; 071010 [生物化学与分子生物学];
摘要
CD69 is involved in immune cell homeostasis, regulating the T cell-mediated immune response through the control of Th17 cell differentiation. However, natural ligands for CD69 have not yet been described. Using recombinant fusion proteins containing the extracellular domain of CD69, we have detected the presence of a ligand(s) for CD69 on human dendritic cells (DCs). Pull-down followed by mass spectrometry analyses of CD69-binding moieties on DCs identified galectin-1 as a CD69 counterreceptor. Surface plasmon resonance and anti-CD69 blocking analyses demonstrated a direct and specific interaction between CD69 and galectin-1 that was carbohydrate dependent. Functional assays with both human and mouse T cells demonstrated the role of CD69 in the negative effect of galectin-1 on Th17 differentiation. Our findings identify CD69 and galectin-1 to be a novel regulatory receptor-ligand pair that modulates Th17 effector cell differentiation and function.
引用
收藏
页码:2479 / 2487
页数:9
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