Cargando…
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...
Autores principales: | , , , , , , , , , , , , , |
---|---|
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 |
_version_ | 1782363148167151616 |
---|---|
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. |
format | Online Article Text |
id | pubmed-4372260 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Cell Press |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT brownchrysothemisc retinoicacidisessentialforth1celllineagestabilityandpreventstransitiontoath17cellprogram AT esterhazydaria retinoicacidisessentialforth1celllineagestabilityandpreventstransitiontoath17cellprogram AT sardeaurelien retinoicacidisessentialforth1celllineagestabilityandpreventstransitiontoath17cellprogram AT londonmariya retinoicacidisessentialforth1celllineagestabilityandpreventstransitiontoath17cellprogram AT pullabhatlavenu retinoicacidisessentialforth1celllineagestabilityandpreventstransitiontoath17cellprogram AT osmagarciaines retinoicacidisessentialforth1celllineagestabilityandpreventstransitiontoath17cellprogram AT albaderraya retinoicacidisessentialforth1celllineagestabilityandpreventstransitiontoath17cellprogram AT ortizcarla retinoicacidisessentialforth1celllineagestabilityandpreventstransitiontoath17cellprogram AT elguetaraul retinoicacidisessentialforth1celllineagestabilityandpreventstransitiontoath17cellprogram AT arnomatthew retinoicacidisessentialforth1celllineagestabilityandpreventstransitiontoath17cellprogram AT derinaldisemanuele retinoicacidisessentialforth1celllineagestabilityandpreventstransitiontoath17cellprogram AT mucidadaniel retinoicacidisessentialforth1celllineagestabilityandpreventstransitiontoath17cellprogram AT lordgrahamm retinoicacidisessentialforth1celllineagestabilityandpreventstransitiontoath17cellprogram AT noellerandolphj retinoicacidisessentialforth1celllineagestabilityandpreventstransitiontoath17cellprogram |