The OT-II model reveals dual in vitro and in vivo immunomodulatory properties of CD6 in T cell activation.
Por:
Leyton-Pereira A, Fernández-Delgado I, Rodríguez-Lagunas MJ, Català C, Casadó-Llombart S, Martin-Cofreces NB, Bustos-Morán E, Jorge Díaz Garrido, Consuegra-Fernández M, Calpena AC, Aranda F, Andrés MV, Baldoma L, Sánchez-Madrid F and Lozano F
Publicada:
26 jun 2025
Ahead of Print:
26 jun 2025
Resumen:
INTRODUCTION: CD6 is a signal transducing transmembrane glycoprotein expressed on T-cells and a subset of B and NK cells that has emerged as a promising therapeutic target in autoimmunity and cancer.The extracellular domain of CD6 interacts with endogenous (CD166/ALCAM, Galectins 1 and 3,CD318/CDCP-1 and CD44) and exogenous (Pathogen-associated Molecular Patterns) ligands, and the phosphorylatable Thr/Ser/Tyr residues of its intracellular region can dock signal transduction effectors.This, together with its physical association with the T cell receptor (TCR) complex at the immunological synapse (IS) supports a relevant immunomodulatory role for CD6 in T cell activation , differentiation and survival. However, activation or inhibitory signalling properties have been observed by CD6 contingent on different experimental settings,rendering its precise function not well understood. METHODS: To ascertain CD6's immunomodulatory role, we investigated the effects of CD6-deficiency in vitro and in vivo under physiological antigen-specific stimulation in TCR transgenic OT-IImice. RESULTS: In vitro ovalbumin (OVA)-specific stimulation of Cd6 (-/-) OT-II splenocytes and in vivo OVA-induced delayed-type hypersensitivity (DTH) supported a negative modulatory role of CD6 in lymphocyte activation. On the contrary, IS studies in Cd6 (-/-) OT-II T cells and OVA-loaded dendritic cells advocate for a positive modulatory role. DISCUSSION: These findings support CD6 as a "dual" immunomodulatory receptor capable of either amplify or attenuate T-cell activation in different experimental contexts. This dual role should be taken into consideration while translating experimental data in to clinical applications, particularly in the development of CD6-targeted therapies for autoimmune disorders and cancer.
Filiaciones:
Leyton-Pereira A:
Immunoreceptors del Sistema Innat i Adaptatiu, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain
Fernández-Delgado I:
Immunology Department, Instituto de Investigación Sanitaria Hospital Universitario La Princesa, Universidad Autónoma de Madrid, Madrid, Spain
Rodríguez-Lagunas MJ:
Departament de Bioquímica i Fisiologia, Facultat de Farmàcia i Ciències de l'Alimentació, Universitat de Barcelona, Barcelona, Spain
Català C:
Immunoreceptors del Sistema Innat i Adaptatiu, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain
Casadó-Llombart S:
Immunoreceptors del Sistema Innat i Adaptatiu, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain
Martin-Cofreces NB:
Immunology Department, Instituto de Investigación Sanitaria Hospital Universitario La Princesa, Universidad Autónoma de Madrid, Madrid, Spain
Videomicroscopy Unit, Instituto de Investigación Sanitaria Hospital Universitario La Princesa, Madrid, Spain
Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV), Madrid, Spain
Bustos-Morán E:
Immunology Department, Instituto de Investigación Sanitaria Hospital Universitario La Princesa, Universidad Autónoma de Madrid, Madrid, Spain
Jorge Díaz Garrido:
Departament de Bioquímica i Fisiologia, Facultat de Farmàcia i Ciències de l'Alimentació, Universitat de Barcelona, Barcelona, Spain
Consuegra-Fernández M:
Immunoreceptors del Sistema Innat i Adaptatiu, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain
Calpena AC:
Department of Pharmacy, Pharmaceutical Technology and Physical Chemistry, Faculty of Pharmacy and Food Sciences, University of Barcelona, Barcelona, Spain
Institute of Nanoscience and Nanotechnology (IN2UB), University of Barcelona, Barcelona, Spain
Aranda F:
Immunoreceptors del Sistema Innat i Adaptatiu, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain
Andrés MV:
Immunoreceptors del Sistema Innat i Adaptatiu, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain
Baldoma L:
Departament de Bioquímica i Fisiologia, Facultat de Farmàcia i Ciències de l'Alimentació, Universitat de Barcelona, Barcelona, Spain
Sánchez-Madrid F:
Immunology Department, Instituto de Investigación Sanitaria Hospital Universitario La Princesa, Universidad Autónoma de Madrid, Madrid, Spain
Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV), Madrid, Spain
Lozano F:
Immunoreceptors del Sistema Innat i Adaptatiu, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain
Servei d'Immunologia, Hospital Clínic de Barcelona, Barcelona, Spain
Departament de Biomedicina, Universitat de Barcelona, Barcelona, Spain
Open Access
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