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Abstract: PO2446

Classical Dendritic Cells Mediate Nephrotoxic Serum Nephritis by Activating T Cells

Session Information

Category: CKD (Non-Dialysis)

  • 2103 CKD (Non-Dialysis): Mechanisms


  • Lu, Xiaohan, Duke University Hospital, Durham, North Carolina, United States
  • Ren, Jiafa, Duke University Hospital, Durham, North Carolina, United States
  • Wen, Yi, Duke University Hospital, Durham, North Carolina, United States
  • Privratsky, Jamie, Duke University Hospital, Durham, North Carolina, United States
  • Crowley, Steven D., Duke University Hospital, Durham, North Carolina, United States

Glomerulonephritis is a prominent cause of chronic kidney disease (CKD) and features robust chronic inflammation. Following an inflammatory insult, myeloid cells infiltrate the kidney and drive CKD progression. Flt3L-expressing classical dendritic cells (DCs) are the most potent antigen-presenting cells, and heterozygous deletion of the ubiquitin editor A20 spontaneously activates DCs. However, the role of Flt3L-expressing classical DCs in the regulation of inflammatory CKD requires elucidation. We hypothesized that classical dendritic cells exacerbate inflammatory kidney injury by promoting the activation of renal T cells.


We induced nephrotoxic serum nephritis (NTS) in flt3L-deficient mice lacking DCs (DC KO), mice with spontaneous DC activation (CD11c Cre+ A20flox/wt = DC ACT), and wild-type (WT) controls. After 14 days of NTS, kidney injury was assessed by pathology scoring and ACRs. In addition, mRNA levels of renal injury biomarkers were determined by RT-PCR and western blot. NTS kidneys were harvested for flow cytometric analysis to determine intra-renal immune cell lineage distributions and test their mRNA levels of inflammatory cytokines.


On day 14 of NTS, DC KO mice had attenuated kidney injury scores compared to WTs (1.6±0.3 vs 3.0±0.3 au, p=0.01), while kidney injury was more severe in DC ACTs than in WTs (2.3±0.3 vs 1.4±0.2 au, p=0.02). Compared to WTs, DC KOs had lower ACRs (432±36 vs 267±11, p=0.001) and reduced renal mRNA levels for NGAL (1.0±0.1 vs 0.2±0.1 au, p=0.001), collagen-I (1.0±0.1 vs 0.4±0.1, p=0.003), and fibronectin (1.0±0.1 vs 0.5±0.1, p=0.01). In contrast, DC ACTs had higher ACRs (623±84 vs 1171±243, p=0.001) and upregulated mRNA for NGAL (29.2±7.4 vs 1.0±0.3 au, p=0.004), collagen-I (6.5±0.9 vs 1.0±0.2, p=0.001), and fibronectin (3.9±0.4 vs. 1.0±0.1, p=0.001). Renal protein levels for collagen-I and fibronectin recapitulated the mRNA patterns. In DC ACT kidneys, absolute numbers of CD8+ effector memory T cells, marked by a CD62LloCD44hi surface expression were higher (2864±648 vs 836±107 cells, p=0.006) and had higher cytokine mRNA levels for TNFα (4.2±0.5 vs 1.0±0.1, p=0.001) and IL1β (2.0±0.3 vs 1.0±0.1, p=0.02) than in WTs at day 14 of NTS.


The pathogenesis of CKD requires classical DC-mediated T cell activation. Inhibition of classical DCs may ameliorate autoimmune nephritis.


  • NIDDK Support