Descripción del proyecto
DENDRITIC CELLS (DCS) ARE ANTIGEN PRESENTING CELLS THAT PLAY A KEY ROLE DURING THE IMMUNE RESPONSE, DCS UNDERGO A DIFFERENTION PROCESS WHEREBY THEY CHANGE FROM WHAT IT IS CALLED "IMMATURE STATE", WHERE THEY PERFORM LARGELY THE ROLE SENTINELS OF INFECTIONS, TO A "MATURE STATE", WHERE THEY PRESENT THE ANTIGENS INCORPORATED IN THE IMMATURE STAGE, TO THE LYMPHOCYTES IN THE LYMPH NODES, DURING THESE TWO DIFFERENTIATION STAGES, DCS EXPRESS CHEMOKINE RECEPTORS AND ARE EXPOSED TO THE CHEMOKINE LIGANDS OF THESE RECEPTORS, CHEMOKINE RECEPTORS, BESIDES CHEMOTAXIS, MAY REGULATE OTHER LEUKOCYTE FUNCTIONS THAT COULD POTENTIALLY CONTRIBUTE TO MODULATE THE IMMUNE RESPONSE, HOWEVER, THIS IS AN ASPECT OF THE PHYSIOLOGY OF DCS THAT HAS BEEN LITTLE STUDIED, TO OBTAIN INFORMATION ON HOW CHEMOKINE RECEPTORS MAY MODULATE THE FUNCTIONS OF DCS WE HAVE SELECTED A SET OF RECEPTORS THAT ARE TYPICAL OF IMMATURE OR MATURE DCS, IN IMMATURE DCS, CCR6 (LIGAND CCL20) AND CXCR4 (LIGAND CXCL12), IN MATURE DCS: CXCR4 (LIGAND CXCL12), CXCR7 (LIGANDS CXCL11 AND CXCL12) AND CCR7 (LIGANDS CCL19 AND CCL21), THIS PROJECT HAS THE FOLLOWING GOALS: (I) IDENTIFY FUNCTIONS, REGULATED BY THE SELECTED CHEMOKINE RECEPTORS, WHICH CAN BE RELEVANT FOR THE CELL ACTIVITIES PERFORMED AT THE MATURATION STAGE OF THE DCS IN WHICH THE RECEPTOR IS EXPRESSED, (II) PROVIDE INFORMATION ON THE MOLECULAR MECHANISMS WHEREBY THE CHEMOKINE RECEPTORS REGULATE THE FUNCTIONS IDENTIFIED, (III) USE ANIMAL MODELS TO ANALYZE THE EFFECT/S THAT THE MANIPULATION OF THESE FUNCTIONS EXERT ON THE IMMUNE RESPONSE, THE INFORMATION OBTAINED WILL CONTRIBUTE TO A BETTER UNDERSTANDING OF THE ROLE OF CHEMOKINE RECEPTORS IN THE REGULATION OF THE IMMUNE RESPONSE, THIS INFORMATION WILL BE USEFUL FOR THE DEVELOPMENT OF PHARMACOLOGICAL STRATEGIES THAT MAY ALLOW TO IMPROVE THIS RESPONSE UNDER NORMAL AND PATHOLOGICAL CONDITIONS, quimioquina\receptor de quimioquinas\célula dendrítica\quimiotaxis\apoptosis