Emergence and suppressive function of Tr1 cells in glomerulonephritis

• DOI: 10.1101/2023.02.07.527417
• Publication Date: 2023-02-08T05:10:10Z
• Authors: Shiwa Soukou-Warg...; Christoph Kilian; Lis Velasquez; Andres Machicote; Franziska Bertram; Friederike Stumme; Tanja Bedke; Anastasios Giannou; Jan Kempski; Morsal Sabihi; Ning Song; Hans-Joachim Paust; Alina Borchers; Laura Garcia Perez; Penelope Pelczar; Beibei Liu; Can Ergen; Babett Steglich; Franziska Muscate; Tobias B. Huber; Ulf Panzer; Nicola Gagliani; Christian F. Krebs; Samuel Huber
• Keywords: 0303 health sciences; 03 medical and health sciences; 3. Good health

Summary T regulatory type 1 (Tr1) cells, which are defined by their function, lack of Foxp3, high expression IL-10, CD49b, and LAG3, known to be able suppress Th1 Th17 in the intestine. cells also main drivers crescentic glomerulonephritis, most severe form renal autoimmune disease. However, whether Tr1 emerge inflammation moreover, they exhibit function during glomerulonephritis has not been thoroughly investigated yet. To address these questions, we used a mouse model experimental double Foxp3 mRFP IL-10 eGFP reporter mice. We found that neg IL-10-producing CD4 + infiltrate kidneys progression. Using single-cell RNA- sequencing, could show express core transcriptional factors characteristic cells. In line with this, showed strong suppressive activity ex vivo were protective . Finally, identify patients anti-neutrophil cytoplasmic autoantibody (ANCA)-associated define profile. currently several immune-mediated inflammatory diseases, e.g. as T- cell therapy. Thus, our study provides proof concept for cell-based therapies glomerulonephritis.