Experimental and genetic evidence for the impact of CD5 and CD6 expression and variation in inflammatory bowel disease
Por:
Casado-Llombart, S, Velasco-de Andres, M, Catala, C, Leyton-Pereira, A, Gutierrez-Cozar, R, Suarez, B, Armiger, N, Carreras, E, Esteller, M, Ricart, E, Ordas, I, Gisbert, JP, Chaparro, M, Esteve, M, Marquez, L, Busquets, D, Iglesias, E, Garcia-Planella, E, Martin-Arranz, MD, Lohmann, J, Ayata, CK, Niess, JH, Engel, P, Panes, J, Salas, A, Domenech, E, Lozano, F
Publicada:
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 I BD 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:
Casado-Llombart, S:
Inst Invest Biomed August Pi & Sunyer IDIBAPS, Immunoreceptors Sistema Innat & Adaptatiu, Barcelona, Spain
Velasco-de Andres, M:
Inst Invest Biomed August Pi & Sunyer IDIBAPS, Immunoreceptors Sistema Innat & Adaptatiu, Barcelona, Spain
Catala, C:
Inst Invest Biomed August Pi & Sunyer IDIBAPS, Immunoreceptors Sistema Innat & Adaptatiu, Barcelona, Spain
Leyton-Pereira, A:
Inst Invest Biomed August Pi & Sunyer IDIBAPS, Immunoreceptors Sistema Innat & Adaptatiu, Barcelona, Spain
Gutierrez-Cozar, R:
Univ Barcelona, Fac Med, Dept Biomed, Barcelona, Spain
Suarez, B:
Hosp Clin Barcelona, Ctr Diagnost Biomed, Serv Immunol, Barcelona, Spain
Armiger, N:
Inst Invest Biomed August Pi & Sunyer IDIBAPS, Immunoreceptors Sistema Innat & Adaptatiu, Barcelona, Spain
Carreras, E:
Inst Invest Biomed August Pi & Sunyer IDIBAPS, Immunoreceptors Sistema Innat & Adaptatiu, Barcelona, Spain
Esteller, M:
Inst Invest Biomed August Pi & Sunyer IDIBAPS, Inflammatory Bowel Dis Grp, Barcelona, Spain
Hosp Clin Barcelona, Gastroenterol Dept, Inflammatory Bowel Dis Unit, Barcelona, Spain
Ctr Invest Biomed Red Enfermedades Hepat & Digest, Madrid, Spain
Ricart, E:
Inst Invest Biomed August Pi & Sunyer IDIBAPS, Inflammatory Bowel Dis Grp, Barcelona, Spain
Hosp Clin Barcelona, Gastroenterol Dept, Inflammatory Bowel Dis Unit, Barcelona, Spain
Ctr Invest Biomed Red Enfermedades Hepat & Digest, Madrid, Spain
Ordas, I:
Inst Invest Biomed August Pi & Sunyer IDIBAPS, Inflammatory Bowel Dis Grp, Barcelona, Spain
Hosp Clin Barcelona, Gastroenterol Dept, Inflammatory Bowel Dis Unit, Barcelona, Spain
Ctr Invest Biomed Red Enfermedades Hepat & Digest, Madrid, Spain
Gisbert, JP:
Ctr Invest Biomed Red Enfermedades Hepat & Digest, Madrid, Spain
Univ Autonoma Madrid UAM, Hosp Univ La Princesa, Inst Invest Sanitaria Princesa IIS IP, Gastroenterol Unit, Madrid, Spain
Chaparro, M:
Ctr Invest Biomed Red Enfermedades Hepat & Digest, Madrid, Spain
Univ Autonoma Madrid UAM, Hosp Univ La Princesa, Inst Invest Sanitaria Princesa IIS IP, Gastroenterol Unit, Madrid, Spain
Esteve, M:
Ctr Invest Biomed Red Enfermedades Hepat & Digest, Madrid, Spain
Hosp Univ Mutua Terrassa, Gastroenterol Dept, Terrassa, Spain
Marquez, L:
Hosp del Mar, Gastroenterol Dept, Barcelona, Spain
Inst Hosp del Mar Invest Med, Barcelona, Spain
Busquets, D:
Hosp Univ Girona Dr Josep Trueta, Dept Gastroenterol, Girona, Spain
Iglesias, E:
Hosp Univ Reina Sofia, Dept Gastroenterol, Cordoba, Spain
Inst Maimonides Invest Biomed Cordoba IMIBIC, Cordoba, Spain
Garcia-Planella, E:
Hosp Santa Creu & Sant Pau, Dept Gastroenterol, Barcelona, Spain
Martin-Arranz, MD:
Univ Autonoma Madrid, La Paz Hosp, Fac Med, IdiPAZ Inst Hlth Res,Dept Gastroenterol, Madrid, Spain
Univ Autonoma Madrid, La Paz Hosp, Fac Med, IdiPAZ Inst Hlth Res,Innate Immun Grp, Madrid, Spain
Lohmann, J:
Univ Bonn, Life & Med Sci LIMES Inst, Bonn, Germany
Ayata, CK:
Univ Basel, Dept Biomed, Basel, Switzerland
Niess, JH:
Univ Basel, Dept Biomed, Basel, Switzerland
St Clara Hosp, Univ Ctr Gastrointestinal & Liver Dis, Basel, Switzerland
Univ Hosp, Basel, Switzerland
Engel, P:
Inst Invest Biomed August Pi & Sunyer IDIBAPS, Immunoreceptors Sistema Innat & Adaptatiu, Barcelona, Spain
Univ Barcelona, Fac Med, Dept Biomed, Barcelona, Spain
Panes, J:
Inst Invest Biomed August Pi & Sunyer IDIBAPS, Inflammatory Bowel Dis Grp, Barcelona, Spain
Hosp Clin Barcelona, Gastroenterol Dept, Inflammatory Bowel Dis Unit, Barcelona, Spain
Ctr Invest Biomed Red Enfermedades Hepat & Digest, Madrid, Spain
Salas, A:
Univ Barcelona, Fac Med, Dept Biomed, Barcelona, Spain
Inst Invest Biomed August Pi & Sunyer IDIBAPS, Inflammatory Bowel Dis Grp, Barcelona, Spain
Ctr Invest Biomed Red Enfermedades Hepat & Digest, Madrid, Spain
Domenech, E:
Ctr Invest Biomed Red Enfermedades Hepat & Digest, Madrid, Spain
Hosp Badalona Germans Trias & Pujol, Gastroenterol Dept, Badalona, Spain
Lozano, F:
Inst Invest Biomed August Pi & Sunyer IDIBAPS, Immunoreceptors Sistema Innat & Adaptatiu, Barcelona, Spain
Univ Barcelona, Fac Med, Dept Biomed, Barcelona, Spain
Hosp Clin Barcelona, Ctr Diagnost Biomed, Serv Immunol, Barcelona, Spain
Green Published, gold, All Open Access, Gold, Green
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