IL-10 control of CD11c+ myeloid cells is essential to maintain immune homeostasis in the small and large intestine

dc.contributor.authorGirard-Madoux, Mathilde J. H.
dc.contributor.authorOber-Blöbaum, Juliane L.
dc.contributor.authorCostes, Léa M. M.
dc.contributor.authorKel, Junda M.
dc.contributor.authorLindenbergh-Kortleve, Dicky J.
dc.contributor.authorBrouwers-Haspels, Inge
dc.contributor.authorHeikema, Astrid P.
dc.contributor.authorSamsom, Janneke N.
dc.contributor.authorClausen, Björn
dc.date.accessioned2022-10-10T08:02:27Z
dc.date.available2022-10-10T08:02:27Z
dc.date.issued2016
dc.description.abstractAlthough IL-10 promotes a regulatory phenotype of CD11c(+) dendritic cells and macrophages in vitro, the role of IL-10 signaling in CD11c(+) cells to maintain intestinal tolerance in vivo remains elusive. To this aim, we generated mice with a CD11c-specific deletion of the IL-10 receptor alpha (Cd11c(cre)Il10ra(fl/fl)). In contrast to the colon, the small intestine of Cd11c(cre)Il10ra(fl/fl) mice exhibited spontaneous crypt hyperplasia, increased numbers of intraepithelial lymphocytes and lamina propria T cells, associated with elevated levels of T cell-derived IFN gamma and IL-17A. Whereas naive mucosal T-cell priming was not affected and oral tolerance to ovalbumin was intact, augmented T-cell function in the lamina propria was associated with elevated numbers of locally dividing T cells, expression of T-cell attracting chemokines and reduced T-cell apoptosis. Upon stimulation, intestinal IL-10Ra deficient CD11c(+) cells exhibited increased activation associated with enhanced IL-6 and TNFa production. Following colonization with Helicobacter hepaticus Cd11c(cre)Il10ra(fl/fl) mice developed severe large intestinal inflammation characterized by infiltrating T cells and increased levels of Il17a, Ifng, and Il12p40. Altogether these findings demonstrate a critical role of IL-10 signaling in CD11c(+) cells to control small intestinal immune homeostasis by limiting reactivation of local memory T cells and to protect against Helicobacter hepaticus-induced colitis.en_GB
dc.description.sponsorshipDFG, Open Access-Publizieren Universität Mainz / Universitätsmedizinde
dc.identifier.doihttp://doi.org/10.25358/openscience-7921
dc.identifier.urihttps://openscience.ub.uni-mainz.de/handle/20.500.12030/7936
dc.language.isoengde
dc.rightsCC-BY-3.0*
dc.rights.urihttps://creativecommons.org/licenses/by/3.0/*
dc.subject.ddc610 Medizinde_DE
dc.subject.ddc610 Medical sciencesen_GB
dc.titleIL-10 control of CD11c+ myeloid cells is essential to maintain immune homeostasis in the small and large intestineen_GB
dc.typeZeitschriftenaufsatzde
jgu.journal.issue22de
jgu.journal.titleOncoTargetde
jgu.journal.volume7de
jgu.organisation.departmentFB 04 Medizinde
jgu.organisation.nameJohannes Gutenberg-Universität Mainz
jgu.organisation.number2700
jgu.organisation.placeMainz
jgu.organisation.rorhttps://ror.org/023b0x485
jgu.pages.end32030de
jgu.pages.start32015de
jgu.publisher.doi10.18632/oncotarget.8337de
jgu.publisher.issn1949-2553de
jgu.publisher.nameImpact Journals LLCde
jgu.publisher.placeS.l.de
jgu.publisher.urihttp://dx.doi.org/10.18632/oncotarget.8337de
jgu.publisher.year2016
jgu.rights.accessrightsopenAccess
jgu.subject.ddccode610de
jgu.type.dinitypeArticleen_GB
jgu.type.resourceTextde
jgu.type.versionPublished versionde
opus.affiliatedClausen, Björn
opus.date.modified2018-08-23T08:23:45Z
opus.identifier.opusid56330
opus.institute.number0458
opus.metadataonlyfalse
opus.organisation.stringFB 04: Medizin: Institut für Molekulare Medizinde_DE
opus.subject.dfgcode00-000
opus.type.contenttypeKeinede_DE
opus.type.contenttypeNoneen_EN

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