April 2014
Volume 55, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2014
Resident Neutrophils Regulate T Cell Activation In The Mouse Model of Dry Eye
Author Affiliations & Notes
  • Yuan Gao
    Vision Science Program, School of Optometry, University of California, Berkeley, Berkeley, CA
  • Jonanthan Jong
    Vision Science Program, School of Optometry, University of California, Berkeley, Berkeley, CA
  • Kyungji Min
    Vision Science Program, School of Optometry, University of California, Berkeley, Berkeley, CA
  • Erick Lu
    Vision Science Program, School of Optometry, University of California, Berkeley, Berkeley, CA
  • Di Wu
    Vision Science Program, School of Optometry, University of California, Berkeley, Berkeley, CA
  • Yibing Zhang
    Vision Science Program, School of Optometry, University of California, Berkeley, Berkeley, CA
  • Karsten Gronert
    Vision Science Program, School of Optometry, University of California, Berkeley, Berkeley, CA
  • Footnotes
    Commercial Relationships Yuan Gao, None; Jonanthan Jong, None; Kyungji Min, None; Erick Lu, None; Di Wu, None; Yibing Zhang, None; Karsten Gronert, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science April 2014, Vol.55, 1875. doi:
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    • Get Citation

      Yuan Gao, Jonanthan Jong, Kyungji Min, Erick Lu, Di Wu, Yibing Zhang, Karsten Gronert; Resident Neutrophils Regulate T Cell Activation In The Mouse Model of Dry Eye. Invest. Ophthalmol. Vis. Sci. 2014;55(13):1875.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: T cells activation and homing is a pivotal event in the sex-specific pathogenesis of Dry Eye Disease (DED). PMN are rate limiting effector cells for generating immune regulatory and anti-inflammatory lipoxins. A key enzyme for the formation of lipoxins is regulated by desiccating stress in the corneal epithelium. Lipoxin formation is down-regulated by estrogen and drives sex-specific differences in corneal wound healing and macrophage responses. We investigated a potential role of PMN and the lipoxin circuit in regulating immune responses in the pathogenesis of DED.

Methods: The standard mouse model of desiccating stress was used to induce DED. Schirmer’s test and clinical fluorescence scoring to visualize ocular surface lesions was used to assess DED. PMNs and CD4+ T cells population were confirmed and quantified by immunohistochemistry, enzymatic assays and flow cytometry in the limbus, lacrimal glands and draining lymph nodes. PMNs were depleted by Ly6g antibody. Lipid mediator formation was quantified by LC/MS/MS-based lipidomics and gene expression quantified by qPCR.

Results: A basal population of tissue PMN is present in the limbus, lacrimal gland and draining lymph nodes of untreated mice. Early events induced by desiccating stress was a marked decrease in basal PMN population in limbus and draining lymph nodes, which was coincident with the appearance of CD4+ T cells. The earliest cellular events triggered by desiccating stress in the lacrimal gland was a 3-fold increase in PMN. PMN depletion prior to inducing DED and reduced basal tissue PMN by 66-84% in the limbus, lacrimal gland and draining lymph nodes and significant decreased in tear production and increased corneal lesions. This PMN depletion correlated with a 3-4-fold increase in CD4+ T cells in limbus and draining lymph nodes after inducing DED. Analysis of PMN dependent lipoxin formation and pathway expression demonstrated activity of the circuit in the cornea, lacrimal gland and draining lymph nodes and this regulatory circuit was significantly impaired in PMN depleted mice.

Conclusions: Tissue PMN patrol the limbus, lacrimal gland and draining lymph nodes and drive formation of anti-inflammatory/immune regulatory lipoxins. Depletion of tissue PMN amplifies DED induced T cell activation. This implicates a novel regulatory role for PMN and the lipoxin circuit in controlling lymphocyte activation in DED.

Keywords: 486 cornea: tears/tear film/dry eye • 557 inflammation • 583 lipids  
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