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

Montes de Oca, Marcela, Kumar, Rajiv, de Labastida Rivera, Fabian, Amante, Fiona H., Sheel, Meru, Faleiro, Rebecca J., Bunn, Patrick T., Best, S.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 and Engwerda, Christian R. (2016) Blimp-1-dependent IL-10 production by Tr1 cells regulates TNF-mediated tissue pathology. PLoS Pathogens, 12 1: 1-21. doi:10.1371/journal.ppat.1005398

Author Montes de Oca, Marcela
Kumar, Rajiv
de Labastida Rivera, Fabian
Amante, Fiona H.
Sheel, Meru
Faleiro, Rebecca J.
Bunn, Patrick T.
Best, S.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.
Title Blimp-1-dependent IL-10 production by Tr1 cells regulates TNF-mediated tissue pathology
Journal name PLoS Pathogens   Check publisher's open access policy
ISSN 1553-7374
Publication date 2016-01-14
Year available 2016
Sub-type Article (original research)
DOI 10.1371/journal.ppat.1005398
Open Access Status DOI
Volume 12
Issue 1
Start page 1
End page 21
Total pages 21
Place of publication San Francisco, CA United States
Publisher Public Library of Science
Collection year 2017
Language eng
Formatted 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 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.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
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