Experimental and genetic evidence for the impact of CD5 and CD6 expression and variation in inflammatory bowel disease.
Por:
Casadó-Llombart S, Velasco-de Andrés M, Català C, Leyton-Pereira A, Gutiérrez-Cózar R, Suárez B, Armiger N, Carreras-Bertran E, Esteller M, Ricart E, Ordás I, Gisbert JP, Chaparro M, Esteve M, Márquez L, Busquets D, Iglesias E, García-Planella E, Martín-Arranz MD, Lohmann J, Ayata CK, Niess JH, Engel P, Panés J, Salas A, Domènech E and Lozano F
Publicada:
21 sep 2022
Ahead of Print:
21 sep 2022
Resumen:
Crohn's disease (CD) and ulcerative colitis (UC) are inflammatory bowel diseases (IBD) resulting from the interaction of multiple environmental, genetic and immunological factors. CD5 and CD6 are paralogs encoding lymphocyte co-receptors involved in fine-tuning intracellular signals delivered upon antigen-specific recognition, microbial pattern recognition and cell adhesion. While CD5 and CD6 expression and variation is known to influence some immune-mediated inflammatory disorders, their role in IBD remains unclear. To this end, Cd5- and Cd6-deficient mice were subjected to dextran sulfate sodium (DSS)-induced colitis, the most widely used experimental animal model of IBD. The two mouse lines showed opposite results regarding body weight loss and disease activity index (DAI) changes following DSS-induced colitis, thus supporting Cd5 and Cd6 expression involvement in the pathophysiology of this experimental IBD model. Furthermore, DNA samples from IBD patients of the ENEIDA registry were used to test association of CD5 (rs2241002 and rs2229177) and CD6 (rs17824933, rs11230563, and rs12360861) single nucleotide polymorphisms with susceptibility and clinical parameters of CD (n=1352) and UC (n=1013). Generalized linear regression analyses showed association of CD5 variation with CD ileal location (rs2241002(CC)) and requirement of biological therapies (rs2241002(C)-rs2229177(T) haplotype), and with poor UC prognosis (rs2241002(T)-rs2229177(T) haplotype). Regarding CD6, association was observed with CD ileal location (rs17824933(G)) and poor prognosis (rs12360861(G)), and with left-sided or extensive UC, and absence of ankylosing spondylitis in IBD (rs17824933(G)). The present experimental and genetic evidence support a role for CD5 and CD6 expression and variation in IBD's clinical manifestations and therapeutic requirements, providing insight into its pathophysiology and broadening the relevance of both immunomodulatory receptors in immune-mediated disorders.
Filiaciones:
Casadó-Llombart S:
Immunoreceptors del Sistema Innat i Adaptatiu, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
Velasco-de Andrés M:
Immunoreceptors del Sistema Innat i Adaptatiu, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
Català C:
Immunoreceptors del Sistema Innat i Adaptatiu, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
Leyton-Pereira A:
Immunoreceptors del Sistema Innat i Adaptatiu, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
Gutiérrez-Cózar R:
Departament de Biomedicina, Facultat de Medicina, Universitat de Barcelona, Barcelona, Spain
Suárez B:
Servei d'Immunologia, Centre de Diagnòstic Biomèdic, Hospital Clínic de Barcelona, Barcelona, Spain
Armiger N:
Immunoreceptors del Sistema Innat i Adaptatiu, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
Carreras-Bertran E:
Immunoreceptors del Sistema Innat i Adaptatiu, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
Esteller M:
Inflammatory Bowel Disease Group, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
Inflammatory Bowel Disease Unit, Gastroenterology Department, Hospital Clínic de Barcelona, Barcelona, Spain
Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain
Ricart E:
Inflammatory Bowel Disease Group, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
Inflammatory Bowel Disease Unit, Gastroenterology Department, Hospital Clínic de Barcelona, Barcelona, Spain
Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain
Ordás I:
Inflammatory Bowel Disease Group, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
Inflammatory Bowel Disease Unit, Gastroenterology Department, Hospital Clínic de Barcelona, Barcelona, Spain
Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain
Gisbert JP:
Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain
Gastroenterology Unit, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IIS-IP), Universidad Autónoma de Madrid (UAM), Madrid, Spain
Chaparro M:
Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain
Gastroenterology Unit, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IIS-IP), Universidad Autónoma de Madrid (UAM), Madrid, Spain
Esteve M:
Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain
Gastroenterology Department, Hospital Universitari Mútua Terrassa, Terrassa, Spain
Márquez L:
Gastroenterology Department, Hospital del Mar and Institut Hospital del Mar Investigacions Mèdiques, Barcelona, Spain
Busquets D:
Department of Gastroenterology, Hospital Universitari de Girona Dr Josep Trueta, Girona, Spain
Iglesias E:
Department of Gastroenterology, Hospital Universitario Reina Sofía, Córdoba, Spain
Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Córdoba, Spain
García-Planella E:
Department of Gastroenterology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
Martín-Arranz MD:
Department of Gastroenterology, and Innate Immunity Group, IdiPAZ Institute for Health Research, La Paz Hospital, Facultad de Medicina, Universidad Autónoma de Madrid, Madrid, Spain
Lohmann J:
Life & Medical Sciences (LIMES) Institute, University of Bonn, Bonn, Germany
Ayata CK:
Department of Biomedicine, University of Basel, Basel, Switzerland
Niess JH:
Department of Biomedicine, University of Basel, Basel, Switzerland
University Center for Gastrointestinal and Liver Diseases, St. Clara Hospital and University Hospital, Basel, Switzerland
Engel P:
Immunoreceptors del Sistema Innat i Adaptatiu, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
Departament de Biomedicina, Facultat de Medicina, Universitat de Barcelona, Barcelona, Spain
Panés J:
Inflammatory Bowel Disease Group, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
Inflammatory Bowel Disease Unit, Gastroenterology Department, Hospital Clínic de Barcelona, Barcelona, Spain
Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain
Salas A:
Departament de Biomedicina, Facultat de Medicina, Universitat de Barcelona, Barcelona, Spain
Inflammatory Bowel Disease Group, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain
Domènech E:
Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain
Gastroenterology Department, Hospital Universitari Germans Trias i Pujol, Badalona, Spain
Lozano F:
Immunoreceptors del Sistema Innat i Adaptatiu, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
Departament de Biomedicina, Facultat de Medicina, Universitat de Barcelona, Barcelona, Spain
Servei d'Immunologia, Centre de Diagnòstic Biomèdic, Hospital Clínic de Barcelona, Barcelona, Spain
Open Access
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