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  • Blimp-1-Dependent IL-10 Production by Tr1 Cells Regulates TNF-Mediated Tissue Pathology

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    Author(s)
    de Oca, Marcela Montes
    Kumar, Rajiv
    Rivera, Fabian de labastida
    Amante, Fiona H
    Sheel, Meru
    Faleiro, Rebecca J
    Bunn, Patrick T
    Best, Shannon E
    Beattie, Lynette
    Ng, Susanna S
    Edwards, Chelsea L
    Muller, Werner
    Cretney, Erika
    Nutt, Stephen L
    Smyth, Mark J
    Haque, Ashraful
    Hill, Geoffrey R
    Sundar, Shyam
    Kallies, Axel
    Engwerda, Christian R
    Griffith University Author(s)
    Ng, Susanna SS.
    Bunn, Patrick
    Engwerda, Christian R.
    Year published
    2016
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    Abstract
    Tumor 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 ...
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    Tumor 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.
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    Journal Title
    PLoS Pathogens
    Volume
    12
    Issue
    1
    DOI
    https://doi.org/10.1371/journal.ppat.1005398
    Copyright Statement
    © 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.
    Subject
    Microbiology not elsewhere classified
    Microbiology
    Immunology
    Medical Microbiology
    Publication URI
    http://hdl.handle.net/10072/142546
    Collection
    • Journal articles

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