Patrolling monocytes promote the pathogenesis of early lupus-like glomerulonephritis
| Autor: | Peter Vogel, Cliff Guy, Heather Tillman, Patrick D. Walker, Hans Häcker, Jeeba Kuriakose, Sirish K. Ippagunta, Vanessa Redecke, Jingran Zhou, Ruiqiong Wu |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Inflammation Monocytes Pathogenesis Mice 03 medical and health sciences 0302 clinical medicine Immune system medicine Animals Humans Adaptor Proteins Signal Transducing Mice Knockout Autoimmune disease Kidney Systemic lupus erythematosus business.industry Toll-Like Receptors Glomerulonephritis General Medicine medicine.disease Lupus Nephritis Disease Models Animal 030104 developmental biology medicine.anatomical_structure 030220 oncology & carcinogenesis Immunology medicine.symptom business Kidney disease |
| Zdroj: | Journal of Clinical Investigation. 129:2251-2265 |
| ISSN: | 1558-8238 0021-9738 |
| DOI: | 10.1172/jci125116 |
| Popis: | Systemic lupus erythematosus (SLE) is a complex autoimmune disease with genetic and environmental contributions. Hallmarks of the disease are the appearance of immune complexes (IC) containing autoreactive Abs and TLR-activating nucleic acids, whose deposition in kidney glomeruli is suspected to promote tissue injury and glomerulonephritis (GN). Here, using a mouse model based on the human SLE susceptibility locus TNFAIP3-interacting protein 1 (TNIP1, also known as ABIN1), we investigated the pathogenesis of GN. We found that GN was driven by TLRs but, remarkably, proceeded independently of ICs. Rather, disease in 3 different mouse models and patients with SLE was characterized by glomerular accumulation of patrolling monocytes (PMos), a cell type with an emerging key function in vascular inflammation. Consistent with such function in GN, monocyte-specific deletion of ABIN1 promoted kidney disease, whereas selective elimination of PMos provided protection. In contrast to GN, PMo elimination did not protect from reduced survival or disease symptoms such as IC generation and splenomegaly, suggesting that GN and other inflammatory processes are governed by distinct pathogenic mechanisms. These data identify TLR-activated PMos as the principal component of an intravascular process that contributes to glomerular inflammation and kidney injury. |
| Databáze: | OpenAIRE |
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