Kidney dendritic cell activation is required for progression of renal disease in a mouse model of glomerular injury

Heymann, Felix, Meyer-Schwesinger, Catherine, Hamilton-Williams, Emma E., Hammerich, Linda, Panzer, Ulf, Kaden, Sylvia, Quaggin, Susan E., Floege, Jurgen, Grone, Hermann-Josef and Kurts, Christian (2009) Kidney dendritic cell activation is required for progression of renal disease in a mouse model of glomerular injury. Journal of Clinical Investigation, 119 5: 1286-1297. doi:10.1172/JCI38399

Author Heymann, Felix
Meyer-Schwesinger, Catherine
Hamilton-Williams, Emma E.
Hammerich, Linda
Panzer, Ulf
Kaden, Sylvia
Quaggin, Susan E.
Floege, Jurgen
Grone, Hermann-Josef
Kurts, Christian
Title Kidney dendritic cell activation is required for progression of renal disease in a mouse model of glomerular injury
Journal name Journal of Clinical Investigation   Check publisher's open access policy
ISSN 0021-9738
Publication date 2009-05
Sub-type Article (original research)
DOI 10.1172/JCI38399
Open Access Status DOI
Volume 119
Issue 5
Start page 1286
End page 1297
Total pages 12
Place of publication Ann Arbor, MI, United States
Publisher American Society for Clinical Investigation
Language eng
Formatted abstract
The progression of kidney disease to renal failure correlates with infiltration of mononuclear immune cells into the tubulointerstitium. These infiltrates contain macrophages, DCs, and T cells, but the role of each cell type in disease progression is unclear. To investigate the underlying immune mechanisms, we generated transgenic mice that selectively expressed the model antigens ovalbumin and hen egg lysozyme in glomerular podocytes (NOH mice). Coinjection of ovalbumin-specific transgenic CD8+ CTLs and CD4+ Th cells into NOH mice resulted in periglomerular mononuclear infiltrates and inflammation of parietal epithelial cells, similar to lesions frequently observed in human chronic glomerulonephritis. Repetitive T cell injections aggravated infiltration and caused progression to structural and functional kidney damage after 4 weeks. Mechanistic analysis revealed that DCs in renal lymph nodes constitutively cross-presented ovalbumin and activated CTLs. These CTLs released further ovalbumin for CTL activation in the lymph nodes and for simultaneous presentation to Th cells by distinct DC subsets residing in the kidney tubulointerstitium. Crosstalk between tubulointerstitial DCs and Th cells resulted in intrarenal cytokine and chemokine production and in recruitment of more CTLs, monocyte-derived DCs, and macrophages. The importance of DCs was established by the fact that DC depletion rapidly resolved established kidney immunopathology. These findings demonstrate that glomerular antigen–specific CTLs and Th cells can jointly induce renal immunopathology and identify kidney DCs as a mechanistic link between glomerular injury and the progression of kidney disease.
Keyword Compartment-Specific Expression
Murine Interstitial Nephritis
Subsets In-Vivo
Crescentic Glomerulonephritis
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
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