Resolution of Autoimmune Uveitis Requires CCL20-Dependent Regulatory T Cells.

Abstract

Uveitis is a leading cause of blindness worldwide and regulatory T cells inversely correlate with uveitis. CCL20 is the chemokine that attracts cells expressing CCR6 and has been shown to be expressed on Tregs. Uveitis patients have a reduced capacity to generate CCR6-expressing Tregs. Using the experimental autoimmune uveitis (EAU) model we examined the effect of a CCL20 deficiency on EAU resolution and the induction and function of Tregs. This report demonstrates that a deficiency in CCL20 delays the resolution of EAU and inhibits the induction of Tregs associated with EAU resolution (post-EAU Tregs). Importantly, a CCL20 deficiency does not impact the capacity of post-EAU Tregs to suppress EAU. The impact of these observations is that if the deficiency preventing the induction of ocular Tregs can be bypassed these Tregs will still be able to function to provide lasting remission of uveitis. This study is the first demonstration that CCL20 is needed for the timely resolution of EAU, that it is required for the generation of post-EAU Tregs, and that CCL20 is not required for post-EAU Tregs to suppress disease, that is, CCL20 is needed for timely resolution of EAU and Treg induction but not function.