Evidence map›Paper›PMID 37315811›Full record

ArticleThe Journal of allergy and clinical immunology2023

IL-4 receptor alpha blockade dampens allergic inflammation and upregulates IL-17A expression to promote Saureus clearance in antigen sensitized mouse skin.

Juan-Manuel Leyva-Castillo, Alex McGurk, Maria Strakosha, Daniela Vega-Mendoza, Sophia E M Smith, Kelsey Stafstrom, Megan Elkins, Janet Chou, Yui-Hsi Wang, Raif S Geha

Open access · bronzeAbstract read
In one paragraph

Article in The Journal of allergy and clinical immunology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed, 1 pooled it
4.0field-weighted citation impact, top 6% 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

9 citing papers in PubMed, 1 synthesis or guideline pooled it, 14 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Keratinocytes: pleiotropic orchestrators of cutaneous immunity and Inflammation - Emerging therapeutic paradigms in dermatological pathologies.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026
    Review
  4. Review
  5. Article
  6. Article
  7. Review
  8. Article
  9. Skin microbiota: pathogenic roles and implications in atopic dermatitis.Frontiers in cellular and infection microbiology · 2024
    Review
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

10 authors at 2 institutions in 2 countries.

Juan-Manuel Leyva-CastilloDivision of Immunology, Boston Children's Hospital and Harvard Medical School, Boston, Mass. Electronic address: Manuel.LeyvaCastillo@childrens.harvard.edu.
Alex McGurkDivision of Immunology, Boston Children's Hospital and Harvard Medical School, Boston, Mass.
Maria StrakoshaDivision of Immunology, Boston Children's Hospital and Harvard Medical School, Boston, Mass.
Daniela Vega-MendozaDivision of Immunology, Boston Children's Hospital and Harvard Medical School, Boston, Mass.
Sophia E M SmithDivision of Immunology, Boston Children's Hospital and Harvard Medical School, Boston, Mass.
Kelsey StafstromDivision of Immunology, Boston Children's Hospital and Harvard Medical School, Boston, Mass.
Megan ElkinsDivision of Immunology, Boston Children's Hospital and Harvard Medical School, Boston, Mass.
Janet ChouDivision of Immunology, Boston Children's Hospital and Harvard Medical School, Boston, Mass.
Yui-Hsi WangSanofi, Cambridge, Mass.
Raif S GehaDivision of Immunology, Boston Children's Hospital and Harvard Medical School, Boston, Mass. Electronic address: raif.geha@childrens.harvard.edu.
Boston Children's Hospital · USSanofi (France) · FR

Funding

Targeted Microbiome Transplant in Atopic DermatitisU19AI117673 · NIAID · NATIONAL JEWISH HEALTH · PI GALLO, RICHARD L · 2015 to 2019
$30.6M
MOLECULAR BASIS OF ALLERGIC AND IMMUNOLOGIC DISEASET32AI007512 · NIAID · CHILDREN'S HOSPITAL BOSTON · PI Janet Chou, Peter A Nigrovic · 1996 to 2026
$13.1M
NIAID NIH HHS T32 AI007512NIAID NIH HHS U19 AI117673
6 · The paper itself

Abstract

backgroundSkin colonization with Staphylococcus aureus aggravates atopic dermatitis and exaggerates allergic skin inflammation in mice. IL-4 receptor α (IL-4Rα) blockade is beneficial in atopic dermatitis and reduces Saureus skin colonization through unknown mechanisms. The cytokine IL-17A restrains Saureus growth.

objectivesThis study sought to examine the effect of IL-4Rα blockade on Saureus colonization at sites of allergic skin inflammation in mice and determine the mechanism involved.

methodsBALB/c mice were epicutaneously sensitized with ovalbumin (OVA). Immediately after, PSVue 794-labeled S aureus strain SF8300 or saline was applied and a single dose of anti-IL-4Rα blocking antibody, a mixture of anti-IL-4Rα and anti-IL-17A blocking antibodies, or IgG isotype controls were administered intradermally. Saureus load was assessed 2 days later by in vivo imaging and enumeration of colony forming units. Skin cellular infiltration was examined by flow cytometry and gene expression by quantitative PCR and transcriptome analysis.

resultsIL-4Rα blockade decreased allergic skin inflammation in OVA-sensitized skin, as well as in OVA-sensitized and Saureus-exposed skin, evidenced by significantly decreased epidermal thickening and reduced dermal infiltration by eosinophils and mast cells. This was accompanied by increased cutaneous expression of Il17a and IL-17A-driven antimicrobial genes with no change in Il4 and Il13 expression. IL-4Rα blockade significantly decreased Saureus load in OVA-sensitized and S aureus-exposed skin. IL-17A blockade reversed the beneficial effect of IL-4Rα blockade on Saureus clearance and reduced the cutaneous expression of IL-17A-driven antimicrobial genes.

conclusionsIL-4Rα blockade promotes Saureus clearance from sites of allergic skin inflammation in part by enhancing IL-17A expression.

Indexed as

Anti-Infective AgentsDermatitis, AtopicAnimalsAntigensInflammationInterleukin-17MiceMice, Inbred BALB COvalbuminReceptors, Interleukin-4SkinAntigensAnti-Infective AgentsInterleukin-17OvalbuminReceptors, Interleukin-4Atopic dermatitisIL-17AIL-4RαSaureustype 2 cytokines

Identifiers

PMID37315811
PMCPMC10592541
OpenAlexW4380301319

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.