Retinoic acid is essential for Th1 cell lineage stability and prevents transition to a Th17 cell program.
Retinoic acid is essential for Th1 cell lineage stability and prevents transition to a Th17 cell program.
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DOI：
10.1016/j.immuni.2015.02.003
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发表时间：
2015-03-17
期刊：
影响因子：
32.4
通讯作者：
Noelle, Randolph J.
中科院分区：
文献类型：
--
作者：
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.
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. Retinoic acid (RA) stabilizes Th1 fate commitment Signaling through RA receptor α (RARα) activates enhancers of Th1-cell-lineage-specifying genes RA-RARα represses Th17-cell genes in Th1 cells and constrains Th1-cell plasticity RA-RARα prevents development of pathogenic Th17 cells in vivo Maintenance of T helper (Th)-cell identity is critical for appropriate immune responses; however, the factors that regulate Th-cell plasticity are unresolved. Brown et al. show that retinoic-acid signaling confers Th1 cell stability and restrains their conversion to Th17 cells.
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影响因子：
32.4
作者：
Hall JA;Cannons JL;Grainger JR;Dos Santos LM;Hand TW;Naik S;Wohlfert EA;Chou DB;Oldenhove G;Robinson M;Grigg ME;Kastenmayer R;Schwartzberg PL;Belkaid Y
通讯作者：
Belkaid Y
DOI：
10.1084/jem.20070663
发表时间：
2007-08-06
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Annunziato F;Cosmi L;Santarlasci V;Maggi L;Liotta F;Mazzinghi B;Parente E;Filì L;Ferri S;Frosali F;Giudici F;Romagnani P;Parronchi P;Tonelli F;Maggi E;Romagnani S
通讯作者：
Romagnani S
影响因子：
4.5
作者：
Cunninghame Graham DS;Morris DL;Bhangale TR;Criswell LA;Syvänen AC;Rönnblom L;Behrens TW;Graham RR;Vyse TJ
通讯作者：
Vyse TJ
影响因子：
30.8
作者：
通讯作者：
--
影响因子：
4
作者：
Kashyap, Vasundhra;Laursen, Kristian B.;Gudas, Lorraine J.
通讯作者：
Gudas, Lorraine J.