Long noncoding RNA MIR4435-2HG enhances metabolic function of myeloid dendritic cells from HIV-1 elite controllers
Name
146136.1-20210416160216-covered-4fa089109ce452e764bbb8648b44a723.pdf
Description
Published version
Size
3.19 MB
Format
Adobe PDF
Checksum (MD5)
f06750a33f0959c5316b1dd159f3c629
Author(s)
Hartana, Ciputra Adijaya
Rassadkina, Yelizaveta
Gao, Ce
Martin-Gayo, Enrique
Walker, Bruce D
Lichterfeld, Mathias
Yu, Xu G
Date Issued
May 3, 2021
Journal
Journal of Clinical Investigation
Publisher
American Society for Clinical Investigation
Version
Final published version
Abstract
Restriction of HIV-1 replication in elite controllers (ECs) is frequently attributed to T cell-mediated immune responses, while the specific contribution of innate immune cells is less clear. Here, we demonstrate an upregulation of the host long noncoding RNA (lncRNA) MIR4435-2HG in primary myeloid dendritic cells (mDCs) from ECs. Elevated expression of this lncRNA in mDCs was associated with a distinct immunometabolic profile, characterized by increased oxidative phosphorylation and glycolysis activities in response to TLR3 stimulation. Using functional assays, we show that MIR4435-2HG directly influenced the metabolic state of mDCs, likely through epigenetic mechanisms involving H3K27ac enrichment at an intronic enhancer in the RPTOR gene locus, the main component of the mammalian target of rapamycin complex 1 (mTORC1). Together, these results suggest a role of MIR4435-2HG for enhancing immunometabolic activities of mDCs in ECs through targeted epigenetic modifications of a member of the mTOR signaling pathway.
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DOI of Published Version
https://doi.org/10.1172/jci146136
