Evidence map›Paper›PMID 22286305›Full record

ArticleNature medicine2012

MicroRNA-21 targets the vitamin D-dependent antimicrobial pathway in leprosy.

Philip T Liu, Matthew Wheelwright, Rosane Teles, Evangelia Komisopoulou, Kristina Edfeldt, Benjamin Ferguson, Manali D Mehta, Aria Vazirnia, Thomas H Rea, Euzenir N Sarno and 2 more

Open access · greenAbstract read
In one paragraph

Article in Nature medicine, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 121 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
121citing papers in PubMed, 1 pooled it
11.6field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

121 citing papers in PubMed, 1 synthesis or guideline pooled it, 209 citations in OpenAlex.

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  18. Nutrients · 2023
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61 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors at 4 institutions in 2 countries.

Philip T LiuOrthopaedic Hospital Research Center, University of California-Los Angeles, Los Angeles, California, USA. ptliu@mednet.ucla.edu
Matthew Wheelwright
Rosane Teles
Evangelia Komisopoulou
Kristina Edfeldt
Benjamin Ferguson
Manali D Mehta
Aria Vazirnia
Thomas H Rea
Euzenir N Sarno
Thomas G Graeber
Robert L Modlin
University of California, Los Angeles · USFundação Oswaldo Cruz · BRInstitute for Molecular Medicine · USUniversity of Southern California · US

Funding

Molecular Analysis of the Host Immune Response in LeprosyR01AI022553 · NIAID · UNIVERSITY OF SOUTHERN CALIFORNIA · PI ROBERT L MODLIN · 1989 to 2026
$15.7M
TCR GAMMA/DELTA LYMPHOCYTES IN HUMAN SKIN LESIONSR01AR040312 · NIAMS · UNIVERSITY OF SOUTHERN CALIFORNIA · PI MODLIN, ROBERT L · 1990 to 2025
$10.4M
ROLE OF TOLL-LIKE RECEPTORS IN SKINR37AI047868 · NIAID · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI MODLIN, ROBERT L · 2000 to 2009
$2.9M
Divergence of Phagocytic and Antimicrobial Programs in LeprosyR01AI047868 · NIAID · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI MODLIN, ROBERT L · 2010 to 2014
$2.4M
Role of Vitamin D Prohormone 25-OHD in the Innate Immune Response to TuberculosisR01AI073539 · NIAID · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI MODLIN, ROBERT L · 2008 to 2012
$2.0M
Application of Novel Antigens and Integrated Microfluidics for Leprosy DiagnosisR01AI082575 · NIAID · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI MODLIN, ROBERT L · 2009 to 2013
$1.7M
Mechanism of retinoic acid receptor induced innate immune responsesK22AI085025 · NIAID · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI LIU, PHILIP T. · 2010 to 2011
$267k
IMMUNOREGULATORY T-LYMPHOCYTES IN LEPROSY SKIN LESIONSR22AI022553 · NIAID · UNIVERSITY OF SOUTHERN CALIFORNIA · PI MODLIN, ROBERT L · 1986 to 1991
–
NIAID NIH HHS AI 022553NIAID NIH HHS AI 047868NIAID NIH HHS AI 073539NIAID NIH HHS K22 AI085025NIAID NIH HHS K22 AI 85025NIAID NIH HHS R01 AI022553NIAID NIH HHS R01 AI047868NIAID NIH HHS R01 AI073539NIAID NIH HHS R01 AI082575NIAID NIH HHS R37 AI047868NIAMS NIH HHS AR 040312NIAMS NIH HHS R01 AR040312
6 · The paper itself

Abstract

Leprosy provides a model to investigate mechanisms of immune regulation in humans, given that the disease forms a spectrum of clinical presentations that correlate with host immune responses. Here we identified 13 miRNAs that were differentially expressed in the lesions of subjects with progressive lepromatous (L-lep) versus the self-limited tuberculoid (T-lep) disease. Bioinformatic analysis revealed a significant enrichment of L-lep-specific miRNAs that preferentially target key immune genes downregulated in L-lep versus T-lep lesions. The most differentially expressed miRNA in L-lep lesions, hsa-mir-21, was upregulated in Mycobacterium leprae-infected monocytes. By directly downregulating Toll-like receptor 2/1 heterodimer (TLR2/1)-induced CYP27B1 and IL1B expression as well as indirectly upregulating interleukin-10 (IL-10), hsa-mir-21 inhibited expression of the genes encoding two vitamin D-dependent antimicrobial peptides, CAMP and DEFB4A. Conversely, knockdown of hsa-mir-21 in M. leprae-infected monocytes enhanced expression of CAMP and DEFB4A and restored TLR2/1-mediated antimicrobial activity against M. leprae. Therefore, the ability of M. leprae to upregulate hsa-mir-21 targets multiple genes associated with the immunologically localized disease form, providing an effective mechanism to escape from the vitamin D-dependent antimicrobial pathway.

Indexed as

25-Hydroxyvitamin D3 1-alpha-HydroxylaseAntimicrobial Cationic Peptidesbeta-DefensinsCells, CulturedHumansInterleukin-10Interleukin-1betaLeprosyLeprosy, LepromatousLeprosy, TuberculoidMicroRNAsMonocytesMycobacterium lepraeSignal TransductionToll-Like Receptor 1Toll-Like Receptor 225-Hydroxyvitamin D3 1-alpha-HydroxylaseAntimicrobial Cationic Peptidesbeta-DefensinsDEFB4A protein, humanInterleukin-10Interleukin-1betaMicroRNAsMIRN21 microRNA, humanToll-Like Receptor 1Toll-Like Receptor 2Vitamin D

Identifiers

PMID22286305
PMCPMC3274599
OpenAlexW2119745788

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.