Refereed journal article or data article (A1)

Long Intergenic Noncoding RNA MIAT as a Regulator of Human Th17 Cell Differentiation




List of AuthorsKhan Mohd Moin, Khan Meraj Hasan, Kalim Ubaid Ullah, Khan Sofia, Junttila Sini, Paulin Niklas, Kong Lingjia, Rasool Omid, Elo Laura L, Lahesmaa Riitta

PublisherFRONTIERS MEDIA SA

Publication year2022

JournalFrontiers in Immunology

Journal name in sourceFRONTIERS IN IMMUNOLOGY

Journal acronymFRONT IMMUNOL

Article number 856762

Volume number13

Number of pages14

ISSN1664-3224

DOIhttp://dx.doi.org/10.3389/fimmu.2022.856762

URLhttps://www.frontiersin.org/articles/10.3389/fimmu.2022.856762/full

Self-archived copy’s web addresshttps://research.utu.fi/converis/portal/detail/Publication/175966383


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 (PKC alpha), 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.

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Last updated on 2023-04-04 at 11:12