@article{bfccb1849a684a988aa4759da8143071,
title = "Retinoic Acid Receptor Alpha Represses a Th9 Transcriptional and Epigenomic Program to Reduce Allergic Pathology",
abstract = "CD4+ T helper (Th) differentiation is regulated by diverse inputs, including the vitamin A metabolite retinoic acid (RA). RA acts through its receptor RARα to repress transcription of inflammatory cytokines, but is also essential for Th-mediated immunity, indicating complex effects of RA on Th specification and the outcome of the immune response. We examined the impact of RA on the genome-wide transcriptional response during Th differentiation to multiple subsets. RA effects were subset-selective and were most significant in Th9 cells. RA globally antagonized Th9-promoting transcription factors and inhibited Th9 differentiation. RA directly targeted the extended Il9 locus and broadly modified the Th9 epigenome through RARα. RA-RARα activity limited murine Th9-associated pulmonary inflammation, and human allergic inflammation was associated with reduced expression of RA target genes. Thus, repression of the Th9 program is a major function of RA-RARα signaling in Th differentiation, arguing for a role for RA in interleukin 9 (IL-9) related diseases.",
keywords = "ATAC-seq, ChIP-seq, Enhancers, Interleukin 9, Interleukins, RNA sequencing, Retinoic acid, T helper cells, Th9 cells, vitamin A",
author = "Schwartz, {Daniella M.} and Farley, {Taylor K.} and Nathan Richoz and Chen Yao and Shih, {Han Yu} and Franziska Petermann and Yuan Zhang and Sun, {Hong Wei} and Erika Hayes and Yohei Mikami and Kan Jiang and Davis, {Fred P.} and Yuka Kanno and Milner, {Joshua D.} and Richard Siegel and Arian Laurence and Fran{\c c}oise Meylan and O'Shea, {John J.}",
note = "Funding Information: We thank J. Simone, J. Lay, and K. Tinsley (NIAMS) for expert assistance in flow cytometry and the NIAMS LACU staff for technical support. We thank C. Liu and F. Zhang (NHLBI) for generating knockout mouse lines. We thank G. Gutierrez-Cruz and S. Dell{\textquoteright}Orso (NIAMS) for deep-sequencing support. This study utilized the high-performance computational capabilities of the Biowulf Linux cluster (NIH). This work was supported by the Intramural Research Programs of NIAMS and NIAID , and by the Office of Dietary Supplements (ODS). Funding Information: We thank J. Simone, J. Lay, and K. Tinsley (NIAMS) for expert assistance in flow cytometry and the NIAMS LACU staff for technical support. We thank C. Liu and F. Zhang (NHLBI) for generating knockout mouse lines. We thank G. Gutierrez-Cruz and S. Dell'Orso (NIAMS) for deep-sequencing support. This study utilized the high-performance computational capabilities of the Biowulf Linux cluster (NIH). This work was supported by the Intramural Research Programs of NIAMS and NIAID, and by the Office of Dietary Supplements (ODS). Publisher Copyright: {\textcopyright} 2018",
year = "2019",
month = jan,
day = "15",
doi = "10.1016/j.immuni.2018.12.014",
language = "English (US)",
volume = "50",
pages = "106--120.e10",
journal = "Immunity",
issn = "1074-7613",
publisher = "Cell Press",
number = "1",
}