Blimp-1-dependent IL-10pProduction by Tr1 cells regulates TNF-mediated tissue pathology

Montes de Oca, M; Kumar, R; de Labastida Rivera, F; Amante, FH; Sheel, M; Faleiro, RJ; Bunn, PT; Best, SE; Beattie, L; Ng, SS; Edwards, CL; Muller, W; Cretney, E; Nutt, SL; Smyth, MJ; Haque, A; Hill, GR; Sundar, S; Kallies, A; Engwerda, CR

Author(s): Montes de Oca, M; Kumar, R; de Labastida Rivera, F; Amante, FH; Sheel, M; Faleiro, RJ; Bunn, PT; Best, SE; Beattie, L; Ng, SS; Edwards, CL; Muller, W; Cretney, E; Nutt, SL; Smyth, MJ; Haque, A; Hill, GR; Sundar, S; Kallies, A; Engwerda, CR;
Details: Publication Year 2016-01,Volume 12,Issue #1,Page e1005398
Journal Title: PLoS Pathog
Publication Type: Journal Article
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 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 IFNgamma-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.
Publisher: PLOS
Research Division(s): Molecular Immunology
PubMed ID: 26765224
Publisher's Version: https://doi.org/10.1371/journal.ppat.1005398
Open Access at Publisher's Site: http://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1005398
Terms of Use/Rights Notice: Refer to copyright notice on published article.
Documents: journal.ppat.1005398.pdf - (6.88MB, application/pdf)

Creation Date: 2016-01-29 11:46:07

Last Modified: 2016-01-29 01:25:56