Evidence map›Paper›PMID 34586363›Full record

ArticleThe Journal of experimental medicine2021

MicroRNA-directed pathway discovery elucidates an miR-221/222-mediated regulatory circuit in class switch recombination.

Eric J Wigton, Yohei Mikami, Ryan J McMonigle, Carlos A Castellanos, Adam K Wade-Vallance, Simon K Zhou, Robin Kageyama, Adam Litterman, Suparna Roy, Daisuke Kitamura and 5 more

Open access · bronzeAbstract read
In one paragraph

Article in The Journal of experimental medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
1.1field-weighted citation impact, top 24% 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

8 citing papers in PubMed, 17 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. The lncRNAeLife · 2023
    Article
  5. Article
  6. Review
  7. Article
  8. Article
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

15 authors at 5 institutions in 2 countries.

Eric J WigtonSandler Asthma Basic Research Center, University of California, San Francisco, San Francisco, CA.ORCID 0000-0001-6111-9433
Yohei MikamiMolecular Immunology and Inflammation Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Rockville, MD.ORCID 0000-0001-5104-4415
Ryan J McMonigleDepartment of Microbiology, University of Alabama at Birmingham, Birmingham, AL.ORCID 0000-0003-0139-5414
Carlos A CastellanosSandler Asthma Basic Research Center, University of California, San Francisco, San Francisco, CA.ORCID 0000-0003-3615-2009
Adam K Wade-VallanceSandler Asthma Basic Research Center, University of California, San Francisco, San Francisco, CA.ORCID 0000-0002-6863-1461
Simon K ZhouSandler Asthma Basic Research Center, University of California, San Francisco, San Francisco, CA.ORCID 0000-0001-8695-7943
Robin KageyamaSandler Asthma Basic Research Center, University of California, San Francisco, San Francisco, CA.ORCID 0000-0002-2865-4976
Adam LittermanSandler Asthma Basic Research Center, University of California, San Francisco, San Francisco, CA.ORCID 0000-0003-3019-9244
Suparna RoySandler Asthma Basic Research Center, University of California, San Francisco, San Francisco, CA.ORCID 0000-0001-9007-8706
Daisuke KitamuraResearch Institute for Biomedical Sciences, Tokyo University of Science, Chiba, Japan.ORCID 0000-0002-5195-0474
Emily C DykhuizenDepartment of Medicinal Chemistry and Molecular Pharmacology, Purdue University, West Lafayette, IN.ORCID 0000-0003-3072-1469
Christopher D C AllenSandler Asthma Basic Research Center, University of California, San Francisco, San Francisco, CA.ORCID 0000-0002-1879-9047
Hui HuDepartment of Microbiology, University of Alabama at Birmingham, Birmingham, AL.ORCID 0000-0002-2915-7189
John J O'SheaMolecular Immunology and Inflammation Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Rockville, MD.ORCID 0000-0002-6456-9752
K Mark AnselSandler Asthma Basic Research Center, University of California, San Francisco, San Francisco, CA.ORCID 0000-0003-4840-9879
University of California, San Francisco · USNational Institutes of Health · USUniversity of Alabama at Birmingham · USPurdue University West Lafayette · USTokyo University of Science · JP

Funding

Role of miRNAs in Th2-Driven inflammation in AsthmaP01HL107202 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI FAHY, JOHN V · 2012 to 2023
$23.3M
Research BaseP30DK063720 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI VAISSE, CHRISTIAN · 2003 to 2019
$21.8M
MEDICAL SCIENTIST TRAINING PROGRAMT32GM008361 · NIGMS · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI YACOUBIAN, TALENE ALENE · 1992 to 2024
$16.8M
MOLECULAR AND CELLULAR IMMUNOLOGYT32AI007334 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI CYSTER, JASON G · 1988 to 2023
$11.0M
ROS Modulation of Innate and Adaptive Immunity in RAP30AR048311 · NIAMS · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI MOUNTZ, JOHN D · 2001 to 2017
$9.5M
Role of miRNAs in Th2-Driven inflammation in AsthmaR01HL109102 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Karl Mark Ansel · 2011 to 2026
$5.5M
Training Program in Rheumatic and Musculoskeletal Diseases ResearchT32AR069516 · NIAMS · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI John D Mountz · 2016 to 2026
$2.6M
The tumor suppressive role of PBRM1, the bromodomain-containing subunit of the PBAF chromatin remodeling complexU01CA207532 · NCI · PURDUE UNIVERSITY · PI DYKHUIZEN, EMILY CARLA · 2017 to 2021
$1.7M
NCI NIH HHS U01 CA207532NHLBI NIH HHS P01 HL107202NHLBI NIH HHS R01 HL109102NIAID NIH HHS T32 AI007334NIAMS NIH HHS P30 AR048311NIAMS NIH HHS T32 AR069516NIDDK NIH HHS P30 DK063720NIGMS NIH HHS T32 GM008361NIH HHS T32AI007334
6 · The paper itself

Abstract

MicroRNAs (miRNAs, miRs) regulate cell fate decisions by post-transcriptionally tuning networks of mRNA targets. We used miRNA-directed pathway discovery to reveal a regulatory circuit that influences Ig class switch recombination (CSR). We developed a system to deplete mature, activated B cells of miRNAs, and performed a rescue screen that identified the miR-221/222 family as a positive regulator of CSR. Endogenous miR-221/222 regulated B cell CSR to IgE and IgG1 in vitro, and miR-221/222-deficient mice exhibited defective IgE production in allergic airway challenge and polyclonal B cell activation models in vivo. We combined comparative Ago2-HITS-CLIP and gene expression analyses to identify mRNAs bound and regulated by miR-221/222 in primary B cells. Interrogation of these putative direct targets uncovered functionally relevant downstream genes. Genetic depletion or pharmacological inhibition of Foxp1 and Arid1a confirmed their roles as key modulators of CSR to IgE and IgG1.

Indexed as

AnimalsB-LymphocytesFemaleGene ExpressionGene Regulatory NetworksHypersensitivityImmunoglobulin Class SwitchingImmunoglobulin EImmunoglobulin GMaleMiceMicroRNAsRecombination, GeneticImmunoglobulin EImmunoglobulin GMicroRNAsMIRN221 microRNA, mouseMIRN222 microRNA, mouse

Identifiers

PMID34586363
PMCPMC8485858
OpenAlexW3203951597

What OpenQuestion holds

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LicenceCC BY-NC-SA
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.