Adoptive Treg Cell Therapy in a Patient With Systemic Lupus Erythematosus

TLDR

Adoptive Treg cell therapy shows promise for autoimmune disease, yet its effects on inflamed tissues remain largely unknown. This study aimed to determine how autologous Treg therapy modulates tissue inflammation in human autoimmune disease, illustrated by a systemic lupus erythematosus patient with active skin lesions. The authors quantified Treg cells and immune activation in blood and skin over time, using deuterium labeling to show transient peripheral blood presence and increased activated Treg percentages in diseased skin. Treg accumulation in skin was associated with dampened interferon‑γ signaling and heightened IL‑17 activity, a shift more pronounced in skin than blood and reproduced in a murine model, indicating that adoptive Treg therapy promotes activated Treg cells and a Th1‑to‑Th17 shift in inflamed tissue.

Abstract

Adoptive Treg cell therapy has great potential to treat autoimmune disease. Currently, very little is known about how these cells impact inflamed tissues. This study was undertaken to elucidate how autologous Treg cell therapy influences tissue inflammation in human autoimmune disease.We describe a systemic lupus erythematosus (SLE) patient with active skin disease who received adoptive Treg therapy. We comprehensively quantified Treg cells and immune activation in peripheral blood and skin, with data obtained at multiple time points posttreatment.Deuterium tracking of infused Treg cells revealed the transient presence of cells in peripheral blood, accompanied by increased percentages of highly activated Treg cells in diseased skin. Flow cytometric analysis and whole transcriptome RNA sequencing revealed that Treg cell accumulation in skin was associated with a marked attenuation of the interferon-γ pathway and a reciprocal augmentation of the interleukin-17 (IL-17) pathway. This phenomenon was more pronounced in skin relative to peripheral blood. To validate these findings, we investigated Treg cell adoptive transfer of skin inflammation in a murine model and found that it also resulted in a pronounced skewing away from Th1 immunity and toward IL-17 production.We report the first case of a patient with SLE treated with autologous adoptive Treg cell therapy. Taken together, our results suggest that this treatment leads to increased activated Treg cells in inflamed skin, with a dynamic shift from Th1 to Th17 responses.