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

PLoS Pathogens
Marcela Montes de OcaChristian R Engwerda

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 I...Continue Reading

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Citations

Feb 1, 2017·Nature Reviews. Immunology·Thomas Korn, Axel Kallies
Dec 4, 2016·The Journal of Immunology : Official Journal of the American Association of Immunologists·Marcela Montes de OcaChristian R Engwerda
Jun 17, 2018·Immunology·Ismail Sebina, Ashraful Haque
Oct 26, 2018·The Journal of Immunology : Official Journal of the American Association of Immunologists·Patrick T BunnChristian R Engwerda
Nov 28, 2018·The Journal of Immunology : Official Journal of the American Association of Immunologists·Mingming SunYingzi Cong
Feb 24, 2019·The Journal of Infectious Diseases·Shashi Bhushan ChauhanChristian Engwerda
Sep 9, 2019·Parasite Immunology·Bhawana SinghChristian Engwerda
May 18, 2020·Parasite Immunology·Satish Chandra PandeyMukesh Samant
Jul 25, 2017·Science Immunology·Ping ZhangGeoffrey R Hill
Sep 25, 2017·Scientific Reports·Rashmi BankotiGislâine A Martins
Mar 29, 2018·Expert Review of Vaccines·Salvador IborraManuel Soto
Apr 27, 2019·Frontiers in Immunology·Emeka B Okeke, Jude E Uzonna
Apr 30, 2019·Frontiers in Immunology·Mohammad AsadNahid Ali
Mar 11, 2020·Nature Communications·Michelle SchorerNicole Joller
Jun 5, 2019·Scientific Reports·Hilmar QuentmeierHans G Drexler
May 15, 2018·The Journal of Infectious Diseases·Chelsea L EdwardsChristian R Engwerda
Nov 22, 2018·Frontiers in Immunology·Chelsea L EdwardsChristian R Engwerda
Nov 2, 2019·Immunological Reviews·Rajiv KumarChristian R Engwerda
Aug 26, 2020·Nature Immunology·Susanna S NgChristian R Engwerda
Feb 28, 2019·Frontiers in Immunology·Rajiv KumarChristian Engwerda
Jul 25, 2017·Journal of Biomedical Science·Shin-Huei FuHuey-Kang Sytwu
Oct 14, 2020·PLoS Pathogens·Marcela Montes de OcaChristian R Engwerda
Dec 22, 2020·Frontiers in Immunology·Joanna McGintyTony J Kenna
Jul 25, 2021·The Journal of Immunology : Official Journal of the American Association of Immunologists·Wenjing YangYingzi Cong
Oct 6, 2021·The Journal of Immunology : Official Journal of the American Association of Immunologists·Sinthuja JegatheeswaranSarah Q Crome

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Methods Mentioned

BETA
transgenic
flow cytometry
electrophoresis
PCR

Software Mentioned

Image Scope
TreeStar
Metamorph
GraphPad Prism
FlowJo

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