ArticleJournal of immunology (Baltimore, Md. : 1950)2015
Female-Specific Downregulation of Tissue Polymorphonuclear Neutrophils Drives Impaired Regulatory T Cell and Amplified Effector T Cell Responses in Autoimmune Dry Eye Disease.
Article in Journal of immunology (Baltimore, Md. : 1950), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers.
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Who cites it
69 citing papers in PubMed, 92 citations in OpenAlex.
- Proresolving mediator profiles in cerebrospinal fluid are linked with disease severity and outcome in adults with tuberculous meningitis.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019Trial
- Corneal Stiffening and Hyperosmolar Stress Associate With YAP1/TAZ Activation and Ocular Surface Inflammation in Dry Eye Disease.Translational vision science & technology · 2026Article
- Neutrophils induce effective antibody responses to the pneumococcal conjugate vaccine by inhibiting T regulatory cells.Journal of leukocyte biology · 2026Article
- Rexinoid NEt-3IB Promotes Resident Macrophage Gene Expression and Mitigates Desiccation-Induced Ocular Surface Disease.Investigative ophthalmology & visual science · 2026Article
- UCMSC-derived exosomes ameliorate dry eye disease pathogenesis by modulating neutrophils on Th17/Treg balance.Scientific reports · 2026Article
- Aging Affects Lipid Homeostasis in Lacrimal Glands by Upregulating Lipogenesis and Changing Its Specificity.Investigative ophthalmology & visual science · 2025Article
- CD4Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- The Impact of Aging on Ocular Diseases: Unveiling Complex Interactions.Aging and disease · 2024Review
- Beyond host defense and tissue injury: the emerging role of neutrophils in tissue repair.American journal of physiology. Cell physiology · 2024Review
- Crosstalk between efferocytic myeloid cells and T-cells and its relevance to atherosclerosis.Frontiers in immunology · 2024Review
- Ocular instillation of conditioned medium from mesenchymal stem cells is effective for dry eye syndrome by improving corneal barrier function.Scientific reports · 2023Article
- Pro- and anti-inflammatory bioactive lipids imbalance contributes to the pathobiology of autoimmune diseases.European journal of clinical nutrition · 2023Review
- Ocular surface immune cell diversity in dry eye disease.Indian journal of ophthalmology · 2023Review
- T-Cell Repertoire Analysis in the Conjunctiva of Murine Dry Eye Model.Investigative ophthalmology & visual science · 2023Article
- Modulation of ocular surface desiccation in a murine model by histatin-5 application.The ocular surface · 2023Article
- OC-01 (Varenicline Solution) Nasal Spray for the Treatment of Dry Eye Disease Signs and Symptoms in Subjects with Autoimmune Disease: Integrated Data from ONSET-1 and ONSET-2.Clinical ophthalmology (Auckland, N.Z.) · 2023Article
- Exogenous Lipoxin A4 attenuates IL4-induced Mucin Expression in Human Airway Epithelial Cells.International journal of medical sciences · 2023Article
- The protective effects of lipoxin A4 on type 2 diabetes mellitus: A Chinese prospective cohort study.Frontiers in endocrinology · 2023Article
- Sex-based differences in conjunctival goblet cell responses to pro-inflammatory and pro-resolving mediators.Scientific reports · 2022Article
- High-Fat Nutritional Challenge Reshapes Circadian Signatures in Murine Extraorbital Lacrimal Glands.Investigative ophthalmology & visual science · 2022Article
9 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Immune-driven dry eye disease primarily affects women; the cause for this sex-specific prevalence is unknown. Polymorphonuclear neutrophils (PMN) have distinct phenotypes that drive inflammation but also regulate lymphocytes and are the rate-limiting cell for generating anti-inflammatory lipoxin A4 (LXA4). Estrogen regulates the LXA4 circuit to induce delayed female-specific wound healing in the cornea. However, the role of PMNs in dry eye disease remains unexplored. We discovered an LXA4-producing tissue PMN population in the corneal limbus, lacrimal glands, and cervical lymph nodes of healthy male and female mice. These tissue PMNs, unlike inflammatory PMNs, expressed a highly amplified LXA4 circuit and were sex-specifically regulated during immune-driven dry eye disease. Desiccating stress in females, unlike in males, triggered a remarkable decrease in lymph node PMN and LXA4 formation that remained depressed during dry eye disease. Depressed lymph node PMN and LXA4 in females correlated with an increase in effector T cells (Th1 and Th17), a decrease in regulatory T cells (Treg), and increased dry eye pathogenesis. Ab depletion of tissue PMN abrogated LXA4 formation in lymph nodes, as well as caused a marked increase in Th1 and Th17 cells and a decrease in Tregs. To establish an immune-regulatory role for PMN-derived LXA4 in dry eye, females were treated with LXA4. LXA4 treatment markedly inhibited Th1 and Th17 and amplified Treg in draining lymph nodes, while reducing dry eye pathogenesis. These results identify female-specific regulation of LXA4-producing tissue PMN as a potential key factor in aberrant effector T cell activation and initiation of immune-driven dry eye disease.
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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.