ArticleJournal of leukocyte biology2016
JAK/STAT regulation of Aspergillus fumigatus corneal infections and IL-6/23-stimulated neutrophil, IL-17, elastase, and MMP9 activity.
Article in Journal of leukocyte biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 45 citations in OpenAlex.
- Invasive aspergillosis in autoimmune inflammatory rheumatic diseases: epidemiology, risk factors, diagnosis, management and challenges.Annals of medicine · 2026Review
- Aging changes the mechanism that underlies JAK2 modulation of neutrophil function.Journal of immunology (Baltimore, Md. : 1950) · 2026Article
- Targeting lactylation in a novel metabolic-epigenetic-inflammatory axis mitigates inflammation and promotes healing following corneal injury.Journal of translational medicine · 2026Article
- P2RX1 in neutrophils mediates JAK/STAT signaling pathway to regulate malignant phenotype of gastric Cancer cells.Molecular genetics and genomics : MGG · 2025Article
- Fungal keratitis caused byIDCases · 2025Article
- Review
- Transcriptional profiling specifies the pathogen-specific human host response to infectious keratitis.Frontiers in cellular and infection microbiology · 2023Article
- Retinoic Acid Receptor-Related Orphan Receptors (RORs) in Eye Development and Disease.Advances in experimental medicine and biology · 2023Review
- Association of Single-Nucleotide Polymorphisms in Interleukin Genes with Microbial Keratitis in a South Indian Population.Pathogens (Basel, Switzerland) · 2022Article
- Evidence of seasonal changes in airborne particulate matter concentration and occupation-specific variations in pulmonary function and haematological parameters among some workers in Enugu Southeast Nigeria: a randomized cross-sectional observational study.Archives of public health = Archives belges de sante publique · 2022Article
- Review
- Cytokine Profile of Invasive Pulmonary Aspergillosis in Severe COVID-19 and Possible Therapeutic Targets.Diagnostics (Basel, Switzerland) · 2022Review
- Article
- Altered molecular pathways and prognostic markers in active systemic juvenile idiopathic arthritis: integrated bioinformatic analysis.Bosnian journal of basic medical sciences · 2022Article
- Article
- Mannan-Binding Lectin Regulates the Th17/Treg Axis Through JAK/STAT and TGF-β/SMAD Signaling AgainstJournal of inflammation research · 2022Article
- A novel 3D culture model of fungal keratitis to explore host-pathogen interactions within the stromal environment.Experimental eye research · 2021Article
- MicroRNA-495 alleviates ulcerative interstitial cystitis via inactivating the JAK-STAT signaling pathway by inhibiting JAK3.International urogynecology journal · 2021Article
- TSLP Produced by Aspergillus fumigatus-Stimulated DCs Promotes a Th17 Response Through the JAK/STAT Signaling Pathway in Fungal Keratitis.Investigative ophthalmology & visual science · 2020Article
- Transcriptome Analysis of the Gene Expression Profiles Associated with Fungal Keratitis in Mice Based on RNA-Seq.Investigative ophthalmology & visual science · 2020Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
IL-6 and IL-23 (IL-6/23) induce IL-17A (IL-17) production by a subpopulation of murine and human neutrophils, resulting in autocrine IL-17 activation, enhanced production of reactive oxygen species, and increased fungal killing. As IL-6 and IL-23 receptors trigger JAK1, -3/STAT3 and JAK2/STAT3 phosphorylation, respectively, we examined the role of this pathway in a murine model of fungal keratitis and also examined neutrophil elastase and gelatinase (matrix metalloproteinase 9) activity by IL-6/23-stimulated human neutrophils in vitro. We found that STAT3 phosphorylation of neutrophils in Aspergillus fumigatus-infected corne as was inhibited by the JAK/STAT inhibitor Ruxolitinib, resulting in impaired fungal killing and decreased matrix metalloproteinase 9 activity. In vitro, we showed that fungal killing by IL-6/23-stimulated human peripheral blood neutrophils was impaired by JAK/STAT inhibitors Ruxolitinib and Stattic, and by the retinoic acid receptor-related orphan receptor γt inhibitor SR1001. This was also associated with decreased reactive oxygen species, IL-17A production, and retinoic acid receptor-related orphan receptor γt translocation to the nucleus. We also demonstrate that IL-6/23-activated neutrophils exhibit increased elastase and gelatinase (matrix metalloproteinase 9) activity, which is inhibited by Ruxolitinib and Stattic but not by SR1001. Taken together, these observations indicate that the regulation of activity of IL-17-producing neutrophils by JAK/STAT inhibitors impairs reactive oxygen species production and fungal killing activity but also blocks elastase and gelatinase activity that can cause tissue damage.
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Registered trials
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.