@article{e52c6e5a6d814c989a422aa094a03d88,
title = "Long Intergenic Noncoding RNA MIAT as a Regulator of Human Th17 Cell Differentiation",
abstract = "T helper 17 (Th17) cells protect against fungal and bacterial infections and are implicated in autoimmunity. Several long intergenic noncoding RNAs (lincRNA) are induced during Th17 differentiation, however, their contribution to Th17 differentiation is poorly understood. We aimed to characterize the function of the lincRNA Myocardial Infarction Associated Transcript (MIAT) during early human Th17 cell differentiation. We found MIAT to be upregulated early after induction of human Th17 cell differentiation along with an increase in the chromatin accessibility at the gene locus. STAT3, a key regulator of Th17 differentiation, directly bound to the MIAT promoter and induced its expression during the early stages of Th17 cell differentiation. MIAT resides in the nucleus and regulates the expression of several key Th17 genes, including IL17A, IL17F, CCR6 and CXCL13, possibly by altering the chromatin accessibility of key loci, including IL17A locus. Further, MIAT regulates the expression of protein kinase C alpha (PKCα), an upstream regulator of IL17A. A reanalysis of published single-cell RNA-seq data showed that MIAT was expressed in T cells from the synovium of RA patients. Our results demonstrate that MIAT contributes to human Th17 differentiation by upregulating several genes implicated in Th17 differentiation. High MIAT expression in T cells of RA patient synovia suggests a possible role of MIAT in Th17 mediated autoimmune pathologies.",
keywords = "gene regulation, long intergenic non-coding, MIAT, RNA-seq, STAT3, Th17 cells, transcription factor",
author = "Khan, {Mohd Moin} and Khan, {Meraj Hasan} and Kalim, {Ubaid Ullah} and Sofia Khan and Sini Junttila and Niklas Paulin and Lingjia Kong and Omid Rasool and Elo, {Laura L.} and Riitta Lahesmaa",
note = "Funding Information: We thank Turku University Hospital, Department of Obstetrics and Gynecology, Maternity Ward, for the cord blood collection. We also thank Marjo Hakkarainen and Sarita Heinonen for their excellent technical help. We duly acknowledge the department{\textquoteright}s core facilities, namely, the Finnish Functional Genomics Centre and Cell Imaging Core Facility supported by Biocenter Finland, for their assistance. The Finnish Centre for Scientific Computing is duly acknowledged for its efficient servers and data analysis resources. Funding Information: MMK was supported by the University of Turku graduate school on Turku Doctoral Programme of Molecular Medicine and a central grant from the Finnish Cultural Foundation. RL was supported by the Academy of Finland, AoF, Centre of Excellence in Molecular Systems Immunology and Physiology Research (2012-2017) grant 250114; by the AoF grants 292335, 294337, 292482, 319280, 329277, 331793, 335435 and 31444; by grants from the JDRF; the Novo Nordisk Foundation (grant NNF19OC0057218); the Sigrid Jus{\'e}lius Foundation; Jane and Aatos Erkko Foundation and the Finnish Cancer Foundation. LLE reports grants from the European Research Council ERC (677943), European Union{\textquoteright}s Horizon 2020 research and innovation programme (675395), Academy of Finland (296801, 304995, 310561, 314443, and 329278), Juvenile Diabetes Research Foundation JDRF (2-2013-32), and Sigrid Juselius Foundation, during the conduct of the study. Our research is also supported by University of Turku, {\AA}bo Akademi University, Turku Graduate School, InFLAMES Flagship Programme of the Academy of Finland (decision number: 337530), Biocenter Finland, and ELIXIR Finland. Publisher Copyright: Copyright {\textcopyright} 2022 Khan, Khan, Kalim, Khan, Junttila, Paulin, Kong, Rasool, Elo and Lahesmaa.",
year = "2022",
month = jun,
day = "15",
doi = "10.3389/fimmu.2022.856762",
language = "English",
volume = "13",
journal = "Frontiers in Immunology",
issn = "1664-3224",
publisher = "Frontiers Media",
}