Tetraspanin CD9 limits mucosal healing in experimental colitis

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dc.contributor.author Saiz, María Laura
dc.contributor.author Cibrian, Danay
dc.contributor.author Ramírez-Huesca, Marta
dc.contributor.author Torralba, Daniel
dc.contributor.author Moreno-Gonzalo, Olga
dc.contributor.author Sánchez-Madrid, Francisco
dc.contributor.other UAM. Departamento de Medicina es_ES
dc.contributor.other Instituto de Investigación Sanitaria Hospital Universitario de La Paz (IdiPAZ) es_ES
dc.date.accessioned 2018-02-28T13:56:21Z
dc.date.available 2018-02-28T13:56:21Z
dc.date.issued 2017-12-19
dc.identifier.citation Frontiers in Immunology 8.DECEMBER (2017): 1854 en_US
dc.identifier.issn 1664-3224 es_ES
dc.identifier.uri http://hdl.handle.net/10486/681331
dc.description.abstract Tetraspanins are a family of proteins with four transmembrane domains that associate between themselves and cluster with other partner proteins, conforming a distinct class of membrane domains, the tetraspanin-enriched microdomains (TEMs). These TEMs constitute macromolecular signaling platforms that regulate key processes in several cellular settings controlling signaling thresholds and avidity of receptors. In this study, we investigated the role of CD9, a tetraspanin that regulates major biological processes such as cell migration and immunological responses, in two mouse models of colitis that have been used to study the pathogenesis of inflammatory bowel disease (IBD). Previous in vitro studies revealed an important role in the interaction of leukocytes with inflamed endothelium, but in vivo evidence of the involvement of CD9 in inflammatory diseases is scarce. Here, we studied the role of CD9 in the pathogenesis of colitis in vivo. Colitis was induced by administration of dextran sodium sulfate (DSS), a chemical colitogen that causes epithelial disruption and intestinal inflammation. CD9 -/- mice showed less severe colitis than wild-type counterparts upon exposure to DSS (2% solution) and enhanced survival in response to a lethal DSS dose (4%). Decreased neutrophil and macrophage cell infiltration was observed in colonic tissue from CD9 -/- animals, in accordance with their lower serum levels of TNF-α, IL-6, and other proinflammatory cytokines in the colon. The specific role of CD9 in IBD was further dissected by transfer of CD4 + CD45RB hi naive T cells into the Rag1 -/- mouse colitis model. However, no significant differences were observed in these settings between both groups, ruling out a role for CD9 in IBD in the lymphoid compartment. Experiments with bone marrow chimeras revealed that CD9 in the non-hematopoietic compartment is involved in colon injury and limits the proliferation of epithelial cells. Our data indicate that CD9 in non-hematopoietic cells plays an important role in colitis by limiting epithelial cell proliferation. Future strategies to repress CD9 expression may be of therapeutic benefit in the treatment of IBD en_US
dc.description.sponsorship This work was supported by grants to FS-M (SAF2014-55579-R; INDISNET-S2011/BMD-2332; ERC-2011-AdG 294340-GENTRIS; PIE13/00041; and CIBER CARDIOVASCULAR) and was cofunded by Fondo Europeo de Desarrollo Regional (FEDER). The CNIC is supported by the Spanish Ministry of Economy, Industry and Competitiveness (MINECO) and by the Pro CNIC Foundation en_US
dc.format.extent 14 pag. es_ES
dc.format.mimetype application/pdf en
dc.language.iso eng en
dc.publisher Frontiers Media en_US
dc.relation.ispartof Frontiers in Immunology en_US
dc.rights © 2017 Saiz, Cibrián, Ramírez-Huesca, Torralba, Moreno-Gonzalo and Sánchez-Madrid. es_ES
dc.subject.other CD9 en_US
dc.subject.other Colitis en_US
dc.subject.other Dextran sodium sulfate en_US
dc.subject.other Mucosal healing en_US
dc.subject.other Tetraspanins en_US
dc.title Tetraspanin CD9 limits mucosal healing in experimental colitis en_US
dc.type article en
dc.subject.eciencia Medicina es_ES
dc.relation.publisherversion http://doi.org/10.3389/fimmu.2017.01854 es_ES
dc.identifier.doi 10.3389/fimmu.2017.01854 es_ES
dc.identifier.publicationfirstpage 1854-1 es_ES
dc.identifier.publicationissue DECEMBRE en_US
dc.identifier.publicationlastpage 1854-14 es_ES
dc.identifier.publicationvolume 8 es_ES
dc.relation.projectID Gobierno de España. SAF2014-55579-R es_ES
dc.relation.projectID Comunidad de Madrid. S2011/BMD-2332/INDESNET es_ES
dc.relation.projectID Gobierno de España. ERC-2011-AdG 294340-GENTRIS es_ES
dc.relation.projectID Gobierno de España. PIE13/00041 es_ES
dc.type.version info:eu-repo/semantics/publishedVersion en
dc.rights.cc Reconocimiento es_ES
dc.rights.accessRights openAccess en
dc.authorUAM Sánchez Madrid, Francisco (259404)

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