Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
  • Clinical Research and Public Health
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All ...
  • Videos
    • Conversations with Giants in Medicine
    • Video Abstracts
  • Reviews
    • View all reviews ...
    • Complement Biology and Therapeutics (May 2025)
    • Evolving insights into MASLD and MASH pathogenesis and treatment (Apr 2025)
    • Microbiome in Health and Disease (Feb 2025)
    • Substance Use Disorders (Oct 2024)
    • Clonal Hematopoiesis (Oct 2024)
    • Sex Differences in Medicine (Sep 2024)
    • Vascular Malformations (Apr 2024)
    • View all review series ...
  • Viewpoint
  • Collections
    • In-Press Preview
    • Clinical Research and Public Health
    • Research Letters
    • Letters to the Editor
    • Editorials
    • Commentaries
    • Editor's notes
    • Reviews
    • Viewpoints
    • 100th anniversary
    • Top read articles

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • Conversations with Giants in Medicine
  • Video Abstracts
  • In-Press Preview
  • Clinical Research and Public Health
  • Research Letters
  • Letters to the Editor
  • Editorials
  • Commentaries
  • Editor's notes
  • Reviews
  • Viewpoints
  • 100th anniversary
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
Long noncoding RNA MIR4435-2HG enhances metabolic function of myeloid dendritic cells from HIV-1 elite controllers
Ciputra Adijaya Hartana, … , Mathias Lichterfeld, Xu G. Yu
Ciputra Adijaya Hartana, … , Mathias Lichterfeld, Xu G. Yu
Published May 3, 2021
Citation Information: J Clin Invest. 2021;131(9):e146136. https://doi.org/10.1172/JCI146136.
View: Text | PDF
Research Article AIDS/HIV Immunology Article has an altmetric score of 59

Long noncoding RNA MIR4435-2HG enhances metabolic function of myeloid dendritic cells from HIV-1 elite controllers

  • Text
  • PDF
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.

Authors

Ciputra Adijaya Hartana, Yelizaveta Rassadkina, Ce Gao, Enrique Martin-Gayo, Bruce D. Walker, Mathias Lichterfeld, Xu G. Yu

×

Figure 3

Upregulation of MIR4435-2HG in mDCs is associated with an enhanced metabolic profile.

Options: View larger image (or click on image) Download as PowerPoint
Upregulation of MIR4435-2HG in mDCs is associated with an enhanced metab...
(A) Flow cytometry contour plots displaying the coexpression of MitoTracker or ROS and activation marker CD86 in mDCs from a representative EC with or without 2 μg/mL Poly(I:C) stimulation for 24 hours. (B) The MFIs of MitoTracker and ROS in total mDCs were compared among ECs (n = 9), HIVNs (n = 8), HAARTs (n = 6), and CPs (n = 9). The MFIs were shown as fold changes after Poly(I:C) stimulation, relative to unstimulated controls. Kruskal-Wallis test was used for statistical analysis. (C, D) The frequencies of mDCs coexpressing MitoTracker or ROS and activation markers (CD86, CD40, and CD83) in ECs (n = 9), HIVNs (n = 8), HAARTs (n = 6), and CPs (n = 9) were compared. The frequencies were expressed as fold changes of respective cell populations after Poly(I:C) stimulation, relative to unstimulated conditions. Kruskal-Wallis test was used to compare the fold changes of cell frequencies among cohorts. *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001.

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts

Picked up by 8 news outlets
Posted by 8 X users
39 readers on Mendeley
See more details