The transcription factor Bhlhe40 is a switch of inflammatory versus antiinflammatory Th1 cell fate determination

The Journal of Experimental Medicine
Fang YuJinfang Zhu

Abstract

Type 1 T helper (Th1) cells play a critical role in host defense against intracellular pathogens and in autoimmune diseases by producing a key inflammatory cytokine interferon (IFN)-γ; some Th1 cells can also be antiinflammatory through producing IL-10. However, the molecular switch for regulating the differentiation of inflammatory and antiinflammatory Th1 cells is still elusive. Here, we show that Bhlhe40-deficient CD4 Th1 cells produced less IFN-γ but substantially more IL-10 than wild-type Th1 cells both in vitro and in vivo. Bhlhe40-mediated IFN-γ production was independent of transcription factor T-bet regulation. Mice with conditional deletion of Bhlhe40 in T cells succumbed to Toxoplasma gondii infection, and blockade of IL-10 signaling during infection rescued these mice from death. Thus, our results demonstrate that transcription factor Bhlhe40 is a molecular switch for determining the fate of inflammatory and antiinflammatory Th1 cells.

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Citations

Oct 16, 2019·The Journal of Experimental Medicine·Margarida SaraivaAnne O'Garra
Aug 23, 2019·Cellular and Molecular Life Sciences : CMLS·Difeng Fang, Jinfang Zhu
Jan 5, 2020·The Journal of Immunology : Official Journal of the American Association of Immunologists·Nicholas N JarjourBrian T Edelson
Aug 30, 2019·Science Translational Medicine·Philip K EhrenbergRasmi Thomas
Apr 24, 2020·The Journal of Immunology : Official Journal of the American Association of Immunologists·Michael L RidleyLeonie S Taams
Jun 9, 2018·The Journal of Experimental Medicine·Leona Gabryšová, Anne O'Garra
Feb 28, 2019·Frontiers in Immunology·Rajiv KumarChristian Engwerda
Dec 14, 2018·Proceedings of the National Academy of Sciences of the United States of America·Feda H Hamdan, Steven A Johnsen
Jan 10, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Yong-Sheng TengYuan Zhuang
Mar 25, 2020·Nature Immunology·Stefan EmmingSilvia Monticelli
Aug 27, 2018·Journal of Leukocyte Biology·Tiffany T LooVanja Lazarevic
Nov 27, 2020·Clinical Microbiology Reviews·Hany M ElsheikhaXing-Quan Zhu
Jul 3, 2019·Cancer Immunology Research·Lei Zhang, Zemin Zhang
Jan 29, 2021·Immunological Reviews·Emina DžafoSilvia Monticelli
Nov 16, 2019·Seminars in Immunology·Christian NeumannSascha Rutz
Nov 1, 2020·International Journal of Molecular Sciences·Xiaoliang Zhu, Jinfang Zhu
Apr 27, 2021·The Journal of Experimental Medicine·Dev BhattWenjun Ouyang
May 28, 2021·Journal of Hepatology·Schalk Van der MerweAgustin Albillos
Jun 22, 2021·International Reviews of Immunology·Kevin M HarrisLinda R Watkins
Jun 29, 2021·Frontiers in Immunology·Ece Canan SayitogluMaria Grazia Roncarolo
Jul 4, 2021·International Immunopharmacology·Ning-Lang YuanDi Zhang
Oct 12, 2020·Trends in Immunology·Melissa E CookBrian T Edelson
Sep 5, 2021·Nature Reviews. Immunology·Lianne KokTon N Schumacher
Sep 23, 2021·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Atif ZafarGanapati H Mahabeleshwar
Nov 5, 2019·Seminars in Immunology·Huiyuan Zhang, Vijay Kuchroo
Oct 5, 2021·Frontiers in Immunology·Aarón Vázquez-JiménezOsbaldo Resendis-Antonio
Oct 9, 2021·The Journal of Clinical Investigation·Romain LévyAnne Puel
Dec 18, 2021·The Journal of Experimental Medicine·René RauschmeierTaras Kreslavsky

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Methods Mentioned

BETA
RNA-Seq
PCR
PMA
ELISA
genotyping

Software Mentioned

Prism
GraphPad
edgeR
bowtie
Excel
FlowJo

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