CCR7 is critical for the induction and maintenance of Th17 immunity in dry eye disease.

PURPOSE 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.

• Publication year

  2014

• Venue

  Investigative Ophthalmology and Visual Science

• Publication date

  2014-08-19

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1167/iovs.14-14481PMID 25139737PMCID PMC4168741
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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