Adoptive Regulatory T Cell Therapy in a Patient with Systemic Lupus Erythematosus

OBJECTIVE:Regulatory T cell (Treg) adoptive cell therapy has great potential to treat autoimmune disease. Currently, very little is known about how these cells impact inflamed tissues. The purpose of this study was to elucidate how autologous Treg therapy influences tissue inflammation in human autoimmune disease. METHODS:We describe a patient with systemic lupus erythematosus (SLE) with active skin disease that received adoptive Treg therapy. We comprehensively quantify Tregs and immune activation in peripheral blood and skin with time post-treatment. RESULTS:Deuterium tracking of infused Tregs revealed the transient presence of cells in peripheral blood accompanied by increased percentages of highly activated Tregs in diseased skin. Flow cytometric analysis and whole transcriptome RNA sequencing (RNAseq) revealed that Treg accumulation in skin was associated with a marked attenuation of the IFNγ pathway and a reciprocal augmentation of the IL-17 pathway. This phenomenon was more pronounced in skin relative to peripheral blood. To validate these findings, we found that Treg adoptive transfer in a murine model of skin inflammation also resulted in a pronounced skewing away from Th1 immunity and towards IL-17 production. CONCLUSIONS:We report the first case of a patient with SLE treated with autologous adoptive Treg therapy. Taken together, our results suggest that this treatment results in increased activated Tregs in inflamed skin with a dynamic shift from Th1 to Th17 responses. This article is protected by copyright. All rights reserved.