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dc.contributor.authorde Oca, Marcela Montes
dc.contributor.authorKumar, Rajiv
dc.contributor.authorRivera, Fabian de labastida
dc.contributor.authorAmante, Fiona H
dc.contributor.authorSheel, Meru
dc.contributor.authorFaleiro, Rebecca J
dc.contributor.authorBunn, Patrick T
dc.contributor.authorBest, Shannon E
dc.contributor.authorBeattie, Lynette
dc.contributor.authorNg, Susanna S
dc.contributor.authorEdwards, Chelsea L
dc.contributor.authorMuller, Werner
dc.contributor.authorCretney, Erika
dc.contributor.authorNutt, Stephen L
dc.contributor.authorSmyth, Mark J
dc.contributor.authorHaque, Ashraful
dc.contributor.authorHill, Geoffrey R
dc.contributor.authorSundar, Shyam
dc.contributor.authorKallies, Axel
dc.contributor.authorEngwerda, Christian R
dc.date.accessioned2018-01-19T06:28:45Z
dc.date.available2018-01-19T06:28:45Z
dc.date.issued2016
dc.identifier.issn1553-7366
dc.identifier.doi10.1371/journal.ppat.1005398
dc.identifier.urihttp://hdl.handle.net/10072/142546
dc.description.abstractTumor necrosis factor (TNF) is critical for controlling many intracellular infections, but can also contribute to inflammation. It can promote the destruction of important cell populations and trigger dramatic tissue remodeling following establishment of chronic disease. Therefore, a better understanding of TNF regulation is needed to allow pathogen control without causing or exacerbating disease. IL-10 is an important regulatory cytokine with broad activities, including the suppression of inflammation. IL-10 is produced by different immune cells; however, its regulation and function appears to be cell-specific and context-dependent. Recently, IL-10 produced by Th1 (Tr1) cells was shown to protect host tissues from inflammation induced following infection. Here, we identify a novel pathway of TNF regulation by IL-10 from Tr1 cells during parasitic infection. We report elevated Blimp-1 mRNA levels in CD4+ T cells from visceral leishmaniasis (VL) patients, and demonstrate IL-12 was essential for Blimp-1 expression and Tr1 cell development in experimental VL. Critically, we show Blimp-1-dependent IL-10 production by Tr1 cells prevents tissue damage caused by IFNγ- dependent TNF production. Therefore, we identify Blimp-1-dependent IL-10 produced by Tr1 cells as a key regulator of TNF-mediated pathology and identify Tr1 cells as potential therapeutic tools to control inflammation.
dc.description.peerreviewedYes
dc.languageEnglish
dc.language.isoeng
dc.publisherPublic Library of Science
dc.relation.ispartofpagefrom1
dc.relation.ispartofpageto21
dc.relation.ispartofissue1
dc.relation.ispartofjournalPLoS Pathogens
dc.relation.ispartofvolume12
dc.subject.fieldofresearchMicrobiology not elsewhere classified
dc.subject.fieldofresearchMicrobiology
dc.subject.fieldofresearchImmunology
dc.subject.fieldofresearchMedical Microbiology
dc.subject.fieldofresearchcode060599
dc.subject.fieldofresearchcode0605
dc.subject.fieldofresearchcode1107
dc.subject.fieldofresearchcode1108
dc.titleBlimp-1-Dependent IL-10 Production by Tr1 Cells Regulates TNF-Mediated Tissue Pathology
dc.typeJournal article
dc.type.descriptionC1 - Articles
dc.type.codeC - Journal Articles
dcterms.licensehttps://creativecommons.org/licenses/by/4.0/
dc.description.versionPublished
gro.rights.copyright© 2016 Montes de Oca et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
gro.hasfulltextFull Text
gro.griffith.authorNg, Susanna SS.
gro.griffith.authorBunn, Patrick
gro.griffith.authorEngwerda, Christian R.


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