Evidence map›Paper›PMID 35660375›Full record

ArticleThe Journal of allergy and clinical immunology2022

Cystatin SN is a potent upstream initiator of epithelial-derived type 2 inflammation in chronic rhinosinusitis.

Angela L Nocera, Sarina K Mueller, Alan D Workman, Dawei Wu, Kristen McDonnell, Peter M Sadow, Mansoor M Amiji, Benjamin S Bleier

Open access · greenAbstract read
In one paragraph

Article in The Journal of allergy and clinical immunology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed, 1 pooled it
6.7field-weighted citation impact, top 2% 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

19 citing papers in PubMed, 1 synthesis or guideline pooled it, 34 citations in OpenAlex.

  1. Roles of Exosomes in Chronic Rhinosinusitis: A Systematic Review.International journal of molecular sciences · 2022
    Pooled it
  2. Trial
  3. Article
  4. Article
  5. Review
  6. Article
  7. Article
  8. Review
  9. Article
  10. Review
  11. Article
  12. The functional role of CST1 and CCL26 in asthma development.Immunity, inflammation and disease · 2024
    Article
  13. Article
  14. Eosinophilic Chronic Rhinosinusitis and Pathogenic Role of Protease.International journal of molecular sciences · 2023
    Review
  15. Review
  16. Article
  17. Article
  18. Article
  19. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors at 3 institutions in 2 countries.

Angela L NoceraDepartment of Otolaryngology, Massachusetts Eye and Ear, Harvard Medical School, Boston, Mass; Department of Pharmaceutical Sciences, School of Pharmacy, Northeastern University, Boston, Mass.
Sarina K MuellerDepartment of Otolaryngology, Massachusetts Eye and Ear, Harvard Medical School, Boston, Mass; Department of Otolaryngology/Head and Neck Surgery, University of Erlangen-Nuremberg, Nuremberg, Germany.
Alan D WorkmanDepartment of Otolaryngology, Massachusetts Eye and Ear, Harvard Medical School, Boston, Mass.
Dawei WuDepartment of Otolaryngology, Massachusetts Eye and Ear, Harvard Medical School, Boston, Mass.
Kristen McDonnellDepartment of Otolaryngology, Massachusetts Eye and Ear, Harvard Medical School, Boston, Mass.
Peter M SadowDepartment of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, Mass.
Mansoor M AmijiDepartment of Pharmaceutical Sciences, School of Pharmacy, Northeastern University, Boston, Mass.
Benjamin S BleierDepartment of Otolaryngology, Massachusetts Eye and Ear, Harvard Medical School, Boston, Mass. Electronic address: benjamin_bleier@meei.harvard.edu.
Massachusetts Eye and Ear Infirmary · USHarvard University · USNortheastern University · US

Funding

Strategies to Overcome Immune Resistance in Head and Neck CancersP01CA240239 · NCI · YALE UNIVERSITY · PI MEMPEL, THORSTEN ROMAN · 2019 to 2023
$8.4M
Direct CNS Delivery System for BDNF AntagoNATs using Heterotopic Mucosal Grafting for the Treatment of Parkinson's DiseaseR01NS108968 · NINDS · MASSACHUSETTS EYE AND EAR INFIRMARY · PI BLEIER, BENJAMIN · 2019 to 2023
$2.5M
NCI NIH HHS P01 CA240239NINDS NIH HHS R01 NS108968
6 · The paper itself

Abstract

backgroundCystatin SN (CST1) and cystatin SA (CST2) are cysteine protease inhibitors that protect against allergen, viral, and bacterial proteases. Cystatins are overexpressed in the setting of allergic rhinitis and chronic rhinosinusitis with nasal polyps (CRSwNP); however, their role in promoting type 2 inflammation remains poorly characterized.

objectiveThe purpose of this study was to use integrated poly-omics and a murine exposure model to explore the link between cystatin overexpression in CRSwNP and type 2 inflammation.

methodsIn this institutional review board- and institutional animal care and use committee-approved study, we compared tissue, exosome, and mucus CST1 and CST2 between CRSwNP and controls (n = 10 per group) by using matched whole exome sequencing, transcriptomic, proteomic, posttranslational modification, histologic, functional, and bioinformatic analyses. C57/BL6 mice were dosed with 3.9 μg/mL of CST1 or PBS intranasally for 5 to 18 days in the presence or absence of epithelial ABCB1a knockdown. Inflammatory cytokines were quantified by using Quansys multiplex assays or ELISAs.

resultsOf the 1305 proteins quantified, CST1 and CST2 were among the most overexpressed protease inhibitors in tissue, exosome, and mucus samples; they were localized to the epithelial layer. Multiple posttranslational modifications were identified in the polyp tissue. Exosomal CST1 and CST2 were strongly and significantly correlated with eosinophils and Lund-Mackay scores. Murine type 2 cytokine secretion and T

conclusionCST1 is a potent upstream initiator of epithelial-derived type 2 inflammation in CRSwNP. Therapeutic strategies targeting CST activity and its associated posttranslational modifications deserve further interrogation.

Indexed as

Nasal PolypsRhinitisSalivary CystatinsSinusitisAllergensAnimalsChronic DiseaseCysteine Proteinase InhibitorsCytokinesInflammationMicePeptide HydrolasesProteomicsAllergensCysteine Proteinase InhibitorsCytokinesPeptide HydrolasesSalivary Cystatinscystatin SAcystatin SNEpitheliumexomeP-glycoproteinposttranslational modificationproteomicssinonasal mucustranscriptome

Identifiers

PMID35660375
PMCPMC9547833
OpenAlexW4281743525

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.