Emergence and suppressive function of Tr1 cells in glomerulonephritis

T regulatory type 1 (Tr1) cells, which are defined by their regulatory function, lack of Foxp3, high expression of IL-10, CD49b and LAG3, are known to be able to suppress Th1 and Th17 in the intestine. Th1 and Th17 cells are among the main drivers of crescentic glomerulonephritis, the most severe form of renal autoimmune disease. However, whether Tr1 cells emerge in renal inflammation or more importantly, whether they exhibit regulatory function during glomerulonephritis is unknown. In order to address these questions, we used a mouse model of experimental crescentic glomerulonephritis and double Foxp3mRFP IL-10eGFP reporter mice. We found that Foxp3neg IL-10- producing CD4+ T cells infiltrate the kidneys during glomerulonephritis progression. Using single cell RNA-sequencing, we could show that these cells express the core transcriptional factors characteristic of Tr1 cells. In line with this, Tr1 cells showed a strong suppressive activity ex vivo, and were protective in experimental crescentic glomerulonephritis in vivo. Finally, we could also identify Tr1 cells in the human kidney of a patient with anti-neutrophil cytoplasmic autoantibody (ANCA)-associated glomerulonephritis, and were able to describe their transcriptional profile. Tr1 cells are currently used in several immune-mediated inflammatory diseases, such as T-cell therapy. Thus, our study sets the premise for Tr1 cell-based therapies in patients with glomerulonephritis. ### Competing Interest Statement The authors have declared no competing interest.