IL-17A-dependent CD4+CD25+ regulatory T cells promote immune privilege of corneal allografts

Khrishen Cunnusamy, Peter W. Chen, Jerry Y. Niederkorn

Research output: Contribution to journalArticle

39 Scopus citations

Abstract

IL-17A is a proinflammatory cytokine that has received attention for its role in the pathogenesis of several autoimmune diseases. IL-17A has also been implicated in cardiac and renal allograft rejection. Accordingly, we hypothesized that depletion of IL-17A would enhance corneal allograft survival. Instead, our results demonstrate that blocking IL-17A in a mouse model of keratoplasty accelerated the tempo and increased the incidence of allograft rejection from 50 to 90%. We describe a novel mechanism by which CD4 +CD25+ regulatory T cells (Tregs) respond to IL-17A and enhance corneal allograft survival. Our findings suggest the following: 1) IL-17A is necessary for ocular immune privilege; 2) IL-17A is not required for the induction of anterior chamber-associated immune deviation; 3) Tregs require IL-17A to mediate a contact-dependent suppression; 4) corneal allograft Tregs suppress the efferent arm of the immune response and are Ag specific; 5) Tregs are not required for corneal allograft survival beyond day 30; and 6) corneal allograft-induced Treg-mediated suppression is transient. Our findings identify IL-17A as a cytokine essential for the maintenance of corneal immune privilege and establish a new paradigm whereby interplay between IL-17A and CD4 +CD25+ Tregs is necessary for survival of corneal allografts.

Original languageEnglish (US)
Pages (from-to)6737-6745
Number of pages9
JournalJournal of Immunology
Volume186
Issue number12
DOIs
StatePublished - Jun 15 2011

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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