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Retinoic Acid Is Essential for Th1 Cell Lineage Stability and Prevents Transition to a Th17 Cell Program

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...

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Autores principales: Brown, Chrysothemis C., Esterhazy, Daria, Sarde, Aurelien, London, Mariya, Pullabhatla, Venu, Osma-Garcia, Ines, al-Bader, Raya, Ortiz, Carla, Elgueta, Raul, Arno, Matthew, de Rinaldis, Emanuele, Mucida, Daniel, Lord, Graham M., Noelle, Randolph J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cell Press 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4372260/
https://www.ncbi.nlm.nih.gov/pubmed/25769610
http://dx.doi.org/10.1016/j.immuni.2015.02.003
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author Brown, Chrysothemis C.
Esterhazy, Daria
Sarde, Aurelien
London, Mariya
Pullabhatla, Venu
Osma-Garcia, Ines
al-Bader, Raya
Ortiz, Carla
Elgueta, Raul
Arno, Matthew
de Rinaldis, Emanuele
Mucida, Daniel
Lord, Graham M.
Noelle, Randolph J.
author_facet Brown, Chrysothemis C.
Esterhazy, Daria
Sarde, Aurelien
London, Mariya
Pullabhatla, Venu
Osma-Garcia, Ines
al-Bader, Raya
Ortiz, Carla
Elgueta, Raul
Arno, Matthew
de Rinaldis, Emanuele
Mucida, Daniel
Lord, Graham M.
Noelle, Randolph J.
author_sort Brown, Chrysothemis C.
collection PubMed
description 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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spelling pubmed-43722602015-04-01 Retinoic Acid Is Essential for Th1 Cell Lineage Stability and Prevents Transition to a Th17 Cell Program Brown, Chrysothemis C. Esterhazy, Daria Sarde, Aurelien London, Mariya Pullabhatla, Venu Osma-Garcia, Ines al-Bader, Raya Ortiz, Carla Elgueta, Raul Arno, Matthew de Rinaldis, Emanuele Mucida, Daniel Lord, Graham M. Noelle, Randolph J. Immunity Article 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. Cell Press 2015-03-17 /pmc/articles/PMC4372260/ /pubmed/25769610 http://dx.doi.org/10.1016/j.immuni.2015.02.003 Text en © 2015 The Authors http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Brown, Chrysothemis C.
Esterhazy, Daria
Sarde, Aurelien
London, Mariya
Pullabhatla, Venu
Osma-Garcia, Ines
al-Bader, Raya
Ortiz, Carla
Elgueta, Raul
Arno, Matthew
de Rinaldis, Emanuele
Mucida, Daniel
Lord, Graham M.
Noelle, Randolph J.
Retinoic Acid Is Essential for Th1 Cell Lineage Stability and Prevents Transition to a Th17 Cell Program
title Retinoic Acid Is Essential for Th1 Cell Lineage Stability and Prevents Transition to a Th17 Cell Program
title_full Retinoic Acid Is Essential for Th1 Cell Lineage Stability and Prevents Transition to a Th17 Cell Program
title_fullStr Retinoic Acid Is Essential for Th1 Cell Lineage Stability and Prevents Transition to a Th17 Cell Program
title_full_unstemmed Retinoic Acid Is Essential for Th1 Cell Lineage Stability and Prevents Transition to a Th17 Cell Program
title_short Retinoic Acid Is Essential for Th1 Cell Lineage Stability and Prevents Transition to a Th17 Cell Program
title_sort retinoic acid is essential for th1 cell lineage stability and prevents transition to a th17 cell program
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4372260/
https://www.ncbi.nlm.nih.gov/pubmed/25769610
http://dx.doi.org/10.1016/j.immuni.2015.02.003
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