Table 4.
Rodent models of renal injury and the effect of DC or Mac depletion
| Mouse model | Phenotype | DC/Mac effect | CD11c-DTR | CD11b-DTR | LipClo |
|---|---|---|---|---|---|
| AKI: | |||||
| UUO | Model of renal fibrosis | CD11b+Gr-1+ or F4/80+ DC interstitial infiltrate | No change in fibrosis79, 80 | Reduced fibrosis6 | Reduced fibrosis 77 |
| IRI | Coagulative necrosis of renal tubular epithelial cells | Neutrophilic, Mac and CD11c+ DC interstitial infiltrate | Exacerbated 68; protection 128 | Exacerbated 68; no change69 | Exacerbated 134; protection 68, 69, 71; decreased TNF production 145 |
| Cisplatin | Renally-excreted drug, concentrated in cortex; predominant damage is to S3 segment of the proximal tubule; coagulative necrosis of RTEC | Not described | At time of cisplatin treatment,- exacerbated injury 127 | Not studied | Not studied |
| Adriamycin | Glomerular capillary permeability, tubular atrophy via ROS | Adoptive transfer of LPS-treated pDC ameliorates disease208 | Not studied | Not studied | Not studied |
| GN: | |||||
| Nephrotoxic | Crescentic GN | DC capture Ag; | At day+4 or | Decreased | Decreased |
| nephritis (NTN) | (see Table 3) | present Ag to T cells | day+10, aggravates renal injury 92; depletion at day+7 reduces injury 90 | glomerular crescents and proteinuria; improved renal function96 | proteinuria 213; prevention of protection by CRP treatment 123 |
| GN (NOH mice) | Podocyte-based glomerular pathology (see Table 3) | CD11c+CD11b+Gr-1+ glomerular infiltrates | Decreased CD11c+CD11b+Gr-1+ glomerular infiltrates | Not studied | Not studied |
| Lupus NZB/W mice | Severe GN with polyI:C 209 | CD11b+GR1-F4/80+ glomerular infiltrates210 | Not studied | Not studied | Decreased accumulation of Mac and glomerular injury 209 |
| MRL.Fas(lpr) mice | See Table 3 | Mature CD11c+ DC within kidney 117; TLR9 expression on DC and Mac in affected glomeruli 211 | Decreased disease severity; autoAb formation (CD11c-DTR mice) 212 | Not studied | Not studied |
| Infection Pyelonephritis | E. coli-induced 70 | DC production of CXCL2 recruits neutrophils 70 | Decreased neutrophil recruitment | Not studied | Not studied |
Abbreviations: AKI – acute kidney injury; BM, bone marrow; CRP – C-reactive protein; GN – glomerulonephritis; IRF – interferon regulatory factor; IRI – ischemia reperfusion injury; LipClo, liposomal clodronate; LPS – lipopolysaccharide; ROS – reactive oxygen species; SIGIRR – single immunoglobulin and toll-interleukin-1 receptor; UUO – unilateral ureteric obstruction