title: CCR7 is critical for the induction and maintenance of Th17 immunity in dry eye disease.
abstract: OBJECTIVE
  We characterized antigen-presenting cell (APC)-relevant chemokine receptor expression in dry eye disease (DED), and investigated the effect of topical CC chemokine receptor (CCR)-7 blockade specifically on Th17 cell immunity and dry eye disease severity.
  
  
  METHODS
  We induced DED in female C57BL/6 mice. Chemokine receptor expression by corneal APCs was characterized using immunohistochemistry. To determine the functional role of CCR7 in DED, mice were treated topically with either anti-CCR7, a control isotype antibody, or left untreated, and clinical disease severity, Th17 responses, and molecular markers of DED were quantified.
  
  
  RESULTS
  Frequencies of CD11b(+) cells and their chemokine expression were increased in the cornea of DED mice. Mice treated topically with anti-CCR7 antibody displayed a significant reduction in clinical disease severity and Th17 response compared to the isotype and untreated groups. Topical CCR7 blockade was effective in ameliorating DED in its acute and chronic stages.
  
  
  CONCLUSIONS
  Our findings suggest that CCR7-mediated trafficking of APCs drives the induction and maintenance of Th17 immunity in DED and that CCR7 blockade is effective in suppressing the immunopathogenic mechanisms in DED.
authors.affiliation: Schepens Eye Research Institute and Massachusetts Eye and Ear Infirmary, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts, United States.
authors.forename: Shilpa
authors.initials: S
authors.lastname: Kodati
authors.affiliation: Schepens Eye Research Institute and Massachusetts Eye and Ear Infirmary, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts, United States.
authors.forename: Sunil K
authors.initials: SK
authors.lastname: Chauhan
authors.affiliation: Schepens Eye Research Institute and Massachusetts Eye and Ear Infirmary, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts, United States.
authors.forename: Yihe
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Schepens Eye Research Institute and Massachusetts Eye and Ear Infirmary, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts, United States.
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Dohlman
authors.affiliation: Schepens Eye Research Institute and Massachusetts Eye and Ear Infirmary, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts, United States.
authors.forename: Parisa
authors.initials: P
authors.lastname: Karimian
authors.affiliation: Schepens Eye Research Institute and Massachusetts Eye and Ear Infirmary, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts, United States.
authors.forename: Daniel
authors.initials: D
authors.lastname: Saban
authors.affiliation: Schepens Eye Research Institute and Massachusetts Eye and Ear Infirmary, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts, United States.
authors.forename: Reza
authors.initials: R
authors.lastname: Dana
mesh_terms: D000818:Animals; D039481:CD11b Antigen / Q000378:metabolism; D003319:Corneal Stroma / Q000166:cytology; D004195:Disease Models, Animal; D015352:Dry Eye Syndromes / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D007150:Immunohistochemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D054400:Receptors, CCR7 / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D058504:Th17 Cells / Q000276:immunology*
chemical_list: D039481:CD11b Antigen; D054400:Receptors, CCR7
keywords: CCR7; Th17; cornea; dry eye