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dc.contributor.authorCebula, Annaen_US
dc.contributor.authorSeweryn, Michalen_US
dc.contributor.authorRempala, Grzegorz A.en_US
dc.contributor.authorPabla, Simarjot Singhen_US
dc.contributor.authorMcIndoe, Richard A.en_US
dc.contributor.authorDenning, Timothy L.en_US
dc.contributor.authorBry, Lynnen_US
dc.contributor.authorKraj, Piotren_US
dc.contributor.authorKisielow, Pawelen_US
dc.contributor.authorIgnatowicz, Leszeken_US
dc.date.accessioned2014-03-11T02:49:35Z
dc.date.issued2013en_US
dc.identifier.citationCebula, Anna, Michal Seweryn, Grzegorz A. Rempala, Simarjot Singh Pabla, Richard A. McIndoe, Timothy L. Denning, Lynn Bry, Piotr Kraj, Pawel Kisielow, and Leszek Ignatowicz. 2013. “Thymus-derived regulatory T cells control tolerance to commensal microbiota.” Nature 497 (7448): 258-262. doi:10.1038/nature12079. http://dx.doi.org/10.1038/nature12079.en
dc.identifier.issn0028-0836en
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:11879147
dc.description.abstractPeripheral mechanisms preventing autoimmunity and maintaining tolerance to commensal microbiota involve CD4+Foxp3+ regulatory T cells1,2 generated in the thymus (tTregs) or extrathymically by induction of naive CD4+Foxp3− T cells (iTregs). Prior studies suggested that the T cell receptor (TCR) repertoires of tTregs and iTregs are biased towards self and non-self antigens, respectively 3–6 but their relative contribution in controlling immunopathology, e.g. colitis and other untoward inflammatory responses triggered by different types of antigens, remains unresolved 7. The intestine, and especially the colon, is a particularly suitable organ to study this question, given the variety of self-, microbiota- and food-derived antigens to which Tregs and other T cell populations are exposed. Intestinal environments can enhance conversion to a regulatory lineage 8,9 and favor tolerogenic presentation of antigens to naive CD4+ T cells 10,11, suggesting that intestinal homeostasis depends on microbiota-specific iTregs 12–15. Here, to identify the origin and antigen-specificity of intestinal Tregs, we performed single cell as well as high-throughput (HT) sequencing of the TCR repertoires of CD4+Foxp3+ and CD4+Foxp3− T cells and analyzed their reactivity against specific commensal species. We show that tTregs constitute the majority of Tregs in all lymphoid and intestinal organs, including colon, where their repertoire is heavily influenced by the composition of the microbiota. Our results suggest that tTregs, and not iTregs, dominantly mediate tolerance to antigens produced by intestinal commensals.en
dc.language.isoen_USen
dc.relation.isversionofdoi:10.1038/nature12079en
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3711137/pdf/en
dash.licenseLAAen_US
dc.titleThymus-derived regulatory T cells control tolerance to commensal microbiotaen
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden
dc.relation.journalNatureen
dash.depositing.authorBry, Lynnen_US
dc.date.available2014-03-11T02:49:35Z
dc.identifier.doi10.1038/nature12079*
dash.contributor.affiliatedBry, Lynn


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