Regulatory role and mechanisms of myeloid TLR4 in anti-GBM glomerulonephritis.

ABSTRACT: Myeloid cells and TLR4 play a critical role in acute kidney injury. This study investigated the regulatory role and mechanisms of myeloid TLR4 in experimental anti-glomerular basement membrane (GBM) glomerulonephritis (GN). Anti-GBM GN was induced in tlr4^flox/flox and tlr4^{flox/flox-lysM-cre} mice by intravenous injection of the sheep anti-mouse GBM antibody. Compared to control mice, conditional disruption of tlr4 from myeloid cells, largely macrophages (> 85%), suppressed glomerular crescent formation and attenuated progressive renal injury by lowering serum creatinine and 24-h urine protein excretion while improving creatinine clearance. Mechanistically, deletion of myeloid tlr4 markedly inhibited renal infiltration of macrophages and T cells and resulted in a shift

SUBMITTER: Yang F 

PROVIDER: S-EPMC8558180 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature