CD4+ T cells produce GM-CSF and drive immune-mediated glomerular disease by licensing monocyte-derived cells to produce MMP12

Despite glomerulonephritis being an immune-mediated disease, the contributions of individual immune cell types are not clear. To address this gap in knowledge, Paust et al. characterized pathological immune cells in samples from patients with glomerulonephritis and in samples from mice with the disease. The authors found that CD4+ T cells producing granulocyte-macrophage colony-stimulating factor (GM-CSF) licensed monocytes to promote disease by producing matrix metalloproteinase 12 and disrupting the glomerular basement membrane. Targeting GM-CSF to inhibit this axis reduced disease severity in mice, implicating this cytokine as a potential therapeutic target for patients with glomerulonephritis

Pathogen-induced tissue-resident memory T(H)17 (T(RM)17) cells amplify autoimmune kidney disease

Although it is well established that microbial infections predispose to autoimmune diseases, the underlying mechanisms remain poorly understood. After infection, tissue-resident memory T (T-RM) cells persist in peripheral organs and provide immune protection against reinfection. However, whether T-RM cells participate in responses unrelated to the primary infection, such as autoimmune inflammation, is unknown. By using high-dimensional single-cell analysis, we identified CD4(+) T-RM cells with a T(H)17 signature (termed T(RM)17 cells) in kidneys of patients with ANCA-associated glomerulonephritis. Experimental models demonstrated that renal T(RM)17 cells were induced by pathogens infecting the kidney, such as Staphylococcus aureus, Candida albicans, and uropathogenic Escherichia coli, and persisted after the clearance of infections. Upon induction of experimental glomerulonephritis, these kidney T(RM)17 cells rapidly responded to local proinflammatory cytokines by producing IL-17A and thereby exacerbate renal pathology. Thus, our data show that pathogen-induced T(RM)17 cells have a previously unrecognized function in aggravating autoimmune disease.erman Research Foundation (DFG) SFB1192 SFB1286 SFBTR57 Deutsche Nierenstiftung Deutsche Gesellschaft fur Nephrologie Werner Otto Stiftung eMed Consortia "Fibromap" from the Federal Ministry of Education and Research Comision Nacional de Investigacion Cientifica y Tecnologica (CONICYT) AFB 170004 Conicyt/FONDEQUIP/EQM140016 Else Kroner-Fresenius Foundatio