Identifying new Treg cells in MS patients

International Congress on Neuroimmunology and Therapeutics

DoubleTree by Hilton Hotel San Francisco Airport, San Francisco, CA, USA

Yawei Liu1, Robert Carlsson1, Manuel Comabella2, Jun Yang Wang1, Michael Kosicki1, Belinda Carrion1, Maruf Hasan1, Xudong Wu1, Xavier Montalban2, Morten Hanefeld Dziegiel3, Finn Sellebjerg1, Per Soelberg Sørensen1, Kristian Helin1 and Shohreh Issazadeh-Navikas1

Posters-Accepted Abstracts: J Neurol Disord

Abstract :

Inflammation is a self-destructive process that can lead to irreversible chronic tissue destruction. The defective generation or function of Tregulatory/Treg cells contributes to chronic autoimmune inflammation. We report the first identification of FoxA1 as a novel transcription factor in T-cells that upon ectopic expression conveys suppressive properties in a new Treg population, hereby called FoxA1+Tregs. FoxA1 bound to the pdl1 promoter, inducing PD-L1, which was essential for FoxA1+Tregs to kill activated T-cells. FoxA1+Tregs had a distinct transcription profile. They express CD4, CD47and PD-L1hi. IFN-β induces FoxA1+Tregs requiring IFNAR signaling; consequently Ifnbâ??/â?? and Ifnarâ??/â?? mice were defective in FoxA1+Tregs. Adoptive transfer of stable FoxA1+Tregs inhibited experimental autoimmune encephalomyelitis mediated by functional FoxA1 and PDL1. In patients with relapsing-remitting multiple sclerosis, response to IFN-β-treatment was associated with expansion of suppressive FoxA1+Tregs. FoxA1 is a lineage-specification factor with a specialized role in supporting differentiation and the suppressive function of FoxA1+Treg cells.