title: The leukocyte activation receptor CD69 controls T cell differentiation through its interaction with galectin-1.
abstract: 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). Pulldown 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.
authors.affiliation: Servicio de Inmunología, Hospital de la Princesa, Universidad Autónoma de Madrid, Instituto Investigación Sanitaria Princesa, Madrid, Spain Department of Vascular Biology and Inflammation, Centro Nacional de Investigaciones Cardiovasculares Carlos III, Madrid, Spain.
authors.forename: Hortensia
authors.initials: H
authors.lastname: de la Fuente
authors.affiliation: Servicio de Inmunología, Hospital de la Princesa, Universidad Autónoma de Madrid, Instituto Investigación Sanitaria Princesa, Madrid, Spain.
authors.forename: Aranzazu
authors.initials: A
authors.lastname: Cruz-Adalia
authors.affiliation: Department of Vascular Biology and Inflammation, Centro Nacional de Investigaciones Cardiovasculares Carlos III, Madrid, Spain.
authors.forename: Gloria
authors.initials: G
authors.lastname: Martinez Del Hoyo
authors.affiliation: Servicio de Inmunología, Hospital de la Princesa, Universidad Autónoma de Madrid, Instituto Investigación Sanitaria Princesa, Madrid, Spain.
authors.forename: Danay
authors.initials: D
authors.lastname: Cibrián-Vera
authors.affiliation: Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Científicas-Universidad Autónoma de Madrid, Cantoblanco, Madrid, Spain.
authors.forename: Pedro
authors.initials: P
authors.lastname: Bonay
authors.affiliation: Laboratory of Cardiovascular Proteomics, Centro Nacional de Investigaciones Cardiovasculares Carlos III, Madrid, Spain.
authors.forename: Daniel
authors.initials: D
authors.lastname: Pérez-Hernández
authors.affiliation: Laboratory of Cardiovascular Proteomics, Centro Nacional de Investigaciones Cardiovasculares Carlos III, Madrid, Spain.
authors.forename: Jesús
authors.initials: J
authors.lastname: Vázquez
authors.affiliation: Cancer Research Program, Hospital del Mar Research Institute, Barcelona, Spain.
authors.forename: Pilar
authors.initials: P
authors.lastname: Navarro
authors.affiliation: Neuroscience Research Program, Hospital del Mar Research Institute, and Pompeu Fabra University, Barcelona, Spain.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Gutierrez-Gallego
authors.affiliation: Department of Vascular Biology and Inflammation, Centro Nacional de Investigaciones Cardiovasculares Carlos III, Madrid, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Ramirez-Huesca
authors.affiliation: Department of Vascular Biology and Inflammation, Centro Nacional de Investigaciones Cardiovasculares Carlos III, Madrid, Spain.
authors.forename: Pilar
authors.initials: P
authors.lastname: Martín
authors.affiliation: Servicio de Inmunología, Hospital de la Princesa, Universidad Autónoma de Madrid, Instituto Investigación Sanitaria Princesa, Madrid, Spain Department of Vascular Biology and Inflammation, Centro Nacional de Investigaciones Cardiovasculares Carlos III, Madrid, Spain fsanchez.hlpr@salud.madrid.org.
authors.forename: Francisco
authors.initials: F
authors.lastname: Sánchez-Madrid
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000276:immunology*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology*; D002448:Cell Adhesion / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology*; D037483:Galectin 1 / Q000276:immunology*; D006801:Humans; D007249:Inflammation / Q000276:immunology; D007371:Interferon-gamma / Q000096:biosynthesis; D020381:Interleukin-17 / Q000096:biosynthesis; D019169:Jurkat Cells; D037181:Lectins, C-Type / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011485:Protein Binding / Q000276:immunology; D011961:Receptors, Fc / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology; D020349:Surface Plasmon Resonance; D058504:Th17 Cells / Q000276:immunology*; D000099192:CD69 Antigens
chemical_list: D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D037483:Galectin 1; D007371:Interferon-gamma; D020381:Interleukin-17; D037181:Lectins, C-Type; D011961:Receptors, Fc; D011993:Recombinant Fusion Proteins; D000099192:CD69 Antigens
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