Expression and variation of lymphocyte scavenger receptors in inflammatory diseases and cancer
- Autores: Sergi Casadó Llombart
- Directores de la Tesis: Francisco Lozano Soto (dir. tes.)
- Lectura: En la Universitat de Barcelona ( España ) en 2021
- Idioma: inglés
- Tribunal Calificador de la Tesis: Marta Alarcón Riquelme (presid.), Concepció Soler Prat (secret.), Eduardo Huarte Sobrino (voc.)
- Programa de doctorado: Programa de Doctorado en Biomedicina por la Universidad de Barcelona
- Materias:
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- Resumen
CD5 and CD6 are cell surface receptors belonging to the scavenger-receptor cysteine-rich superfamily. They are expressed on T and B1a lymphocytes, as well as on some other cell subtypes. Both molecules bind to the clonotypic lymphocyte receptors of T (TCR)and B (BCR) cells and are well suited to modulate their signaling. Previous studies show they play relevant roles during lymphocyte activation, and therefore in T cell maturation, tolerance, and several immune-mediated disorders. This suggest that both CD5 and CD6 might be considered as immune checkpoints, but there is no consensus in this aspect. The objective of the present thesis was to further explore the modulatory properties of CD5 and CD6, by studying the role of their expression and genetic variation in experimental models and patient cohorts of immune-mediated diseases. First the role of CD5 and CD6 expression was explored by subjecting CD5-or CD6-deficient mice (Cd5-/-, Cd6-/-, respectively) to dextran sulphate sodium-induced colitis. Cd5-/-mice showed a milder colitis phenotype than wild type counterparts, whereas Cd6-/-mice showed a more severe phenotype. A mechanistic study pointed towards a defect in the natural killer cell function in Cd6-/-mice, resulting in increased neutrophil-mediateddamage. Then, the effect of single nucleotide polymorphisms (SNPs) located in the CD5and CD6loci was assessed in cohorts of patients undergoing immune-mediated diseases. CD5, CD6and CD166/ALCAM(a well described CD6 ligand) SNPs and haplotypes were found to impact the clinical course of immune-mediated inflammatory diseases (inflammatory bowel disease, primary Sjögren’s syndrome) and cancer (prostate cancer). The results highlight the relevance of CD5 and CD6 expression and variation in inflammatory diseases and cancer, two sides of the same coin, and are in line with previous reports. This evidence favors the idea of classifying CD5 and CD6 as immune checkpoints, and grants them interest as possible new markers or therapeutic targets in immune-mediated disorders.
