The OT-II model reveals dual in vitro and in vivo immunomodulatory properties of CD6 in T cell activation.
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-...
| Autores: | , , , , , , , , , , , , , , |
|---|---|
| Tipo de recurso: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2025 |
| País: | España |
| Institución: | Fundació Sant Joan de Déu |
| Repositorio: | r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déu |
| OAI Identifier: | oai:fsjd.fundanetsuite.com:p29199 |
| Acceso en línea: | https://fsjd.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=29199 |
| Access Level: | acceso abierto |
| Palabra clave: | CD6 deficiency delayed T cell-mediated hypersensitivity immunological synapse immunomodulation lymphocyte activation lymphocyte scavenger receptors |
| Sumario: | 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. |
|---|