Retinoic acid is essential for Th1 cell lineage stability and prevents transition to a Th17 cell program

Immunity
Chrysothemis C BrownRandolph J Noelle

Abstract

CD4(+) T cells differentiate into phenotypically distinct T helper cells upon antigenic stimulation. Regulation of plasticity between these CD4(+) T-cell lineages is critical for immune homeostasis and prevention of autoimmune disease. However, the factors that regulate lineage stability are largely unknown. Here we investigate a role for retinoic acid (RA) in the regulation of lineage stability using T helper 1 (Th1) cells, traditionally considered the most phenotypically stable Th subset. We found that RA, through its receptor RARα, sustains stable expression of Th1 lineage specifying genes, as well as repressing genes that instruct Th17-cell fate. RA signaling is essential for limiting Th1-cell conversion into Th17 effectors and for preventing pathogenic Th17 responses in vivo. Our study identifies RA-RARα as a key component of the regulatory network governing maintenance and plasticity of Th1-cell fate and defines an additional pathway for the development of Th17 cells.

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Citations

Feb 16, 2016·Nature Reviews. Immunology·Michel DuPage, Jeffrey A Bluestone
Sep 17, 2015·International Immunology·Serge A van de Pavert, Eric Vivier
Mar 24, 2016·Mucosal Immunology·A SamarakoonP Johnson
Mar 27, 2015·European Journal of Immunology·Chrysothemis C Brown, Randolph J Noelle
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May 12, 2016·Annual Review of Immunology·Alexandre Larange, Hilde Cheroutre
Jun 16, 2016·Nutrients·Maria Rosa BonoDaniela Sauma
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Feb 25, 2017·Parasite Immunology·T Shea-DonohueA Smith
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May 16, 2017·Nature Reviews. Immunology·Lisa A Reynolds, B Brett Finlay
Apr 4, 2017·Parasite Immunology·N Powell, T T MacDonald
Dec 20, 2016·Arthritis & Rheumatology·Sabrina CeerazRandolph J Noelle
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Jun 30, 2015·Nature Medicine·Marc Veldhoen, Cristina Ferreira
Oct 1, 2019·Immunology·Alessio MazzoniFrancesco Annunziato
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Methods Mentioned

BETA
FACS
ChIP
ChIP-seq
transgenically
Flow Cytometry
chips
Immunoprecipitation

Software Mentioned

Flowjo
Active Motif
Graphpad Prism

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