Evidence map›Paper›PMID 31996771›Full record

ArticleScientific reports2020

Cathepsin S activation contributes to elevated CX3CL1 (fractalkine) levels in tears of a Sjögren's syndrome murine model.

Runzhong Fu, Hao Guo, Srikanth Janga, Minchang Choi, Wannita Klinngam, Maria C Edman, Sarah F Hamm-Alvarez

Abstract read
In one paragraph

Article in Scientific reports, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
–field-weighted citation impact
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. Review
  2. Article
  3. Microbiology spectrum · 2025
    Article
  4. Review
  5. Review
  6. Article
  7. Review
  8. Article
  9. Article
  10. Article
  11. Review
  12. Early Dry Eye Disease Onset in a NOD.H-2h4 Mouse Model of Sjögren's Syndrome.Investigative ophthalmology & visual science · 2022
    Article
  13. Article
  14. Article
  15. Targeted Therapy for Primary Sjögren's Syndrome: Where are We Now?BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2021
    Review
  16. Article
  17. Rab27a Contributes to Cathepsin S Secretion in Lacrimal Gland Acinar Cells.International journal of molecular sciences · 2021
    Article
  18. Article
  19. 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

7 authors.

Runzhong FuDepartment of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, Roski Eye Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA, 90033, USA.
Hao GuoDepartment of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, Roski Eye Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA, 90033, USA.
Srikanth JangaDepartment of Ophthalmology, Roski Eye Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA, 90033, USA.
Minchang ChoiDepartment of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, Roski Eye Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA, 90033, USA.
Wannita KlinngamDepartment of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, Roski Eye Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA, 90033, USA.
Maria C EdmanDepartment of Ophthalmology, Roski Eye Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA, 90033, USA.
Sarah F Hamm-AlvarezDepartment of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, Roski Eye Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA, 90033, USA. shalvar@usc.edu.

Funding

Research Supplements to Promote DiversityR01EY011386 · NEI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI HAMM-ALVAREZ, SARAH F · 1996 to 2025
$9.3M
Ophthalmic Therapeutics Engineering CoreP30EY029220 · NEI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI Mahnaz Shahidi · 2018 to 2026
$6.5M
NEI NIH HHS P30 EY029220NEI NIH HHS R01 EY011386
6 · The paper itself

Abstract

Autoimmune dacryoadenitis and altered lacrimal gland (LG) secretion are features of Sjögren's syndrome (SS). Activity of cathepsin S (CTSS), a cysteine protease, is significantly and specifically increased in SS patient tears. The soluble chemokine, CX3CL1 (fractalkine), is cleaved from membrane-bound CX3CL1 by proteases including CTSS. We show that CX3CL1 is significantly elevated by 2.5-fold in tears (p = 0.0116) and 1.4-fold in LG acinar cells (LGAC)(p = 0.0026) from male NOD mice, a model of autoimmune dacryoadenitis in SS, relative to BALB/c controls. Primary mouse LGAC and human corneal epithelial cells (HCE-T cells) exposed to interferon-gamma, a cytokine elevated in SS, showed up to 9.6-fold (p ≤ 0.0001) and 25-fold (p ≤ 0.0001) increases in CX3CL1 gene expression, and 1.9-fold (p = 0.0005) and 196-fold (p ≤ 0.0001) increases in CX3CL1 protein expression, respectively. Moreover, exposure of HCE-T cells to recombinant human CTSS at activity equivalent to that in SS patient tears increased cellular CX3CL1 gene and protein expression by 2.8-fold (p = 0.0021) and 5.1-fold (p ≤ 0.0001), while increasing CX3CL1 in culture medium by 5.8-fold (p ≤ 0.0001). Flow cytometry demonstrated a 4.5-fold increase in CX3CR1-expressing immune cells (p ≤ 0.0001), including increased T-cells and macrophages, in LG from NOD mice relative to BALB/c. CTSS-mediated induction/cleavage of CX3CL1 may contribute to ocular surface and LG inflammation in SS.

Indexed as

AnimalsCathepsinsCells, CulturedChemokine CX3CL1DacryocystitisDisease Models, AnimalEpithelium, CornealHumansInterferon-gammaLacrimal ApparatusMaleMiceMice, Inbred BALB CMice, Inbred NODSjogren's SyndromeTearscathepsin SCathepsinsChemokine CX3CL1Interferon-gamma

Identifiers

PMID31996771
PMCPMC6989636

What OpenQuestion holds

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Registered trials

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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.