Increased tubulointerstitial recruitment of human CD141hi CLEC9A+ and CD1c+ myeloid dendritic cell subsets in renal fibrosis and chronic kidney disease

Kassianos, Andrew J., Wang, Xiangju, Sampangi, Sandeep, Muczynski, Kimberly, Healy, Helen and Wilkinson, Ray (2013) Increased tubulointerstitial recruitment of human CD141hi CLEC9A+ and CD1c+ myeloid dendritic cell subsets in renal fibrosis and chronic kidney disease. American Journal of Physiology - Renal Physiology, 305 10: F1391-F1401. doi:10.1152/ajprenal.00318.2013


Author Kassianos, Andrew J.
Wang, Xiangju
Sampangi, Sandeep
Muczynski, Kimberly
Healy, Helen
Wilkinson, Ray
Title Increased tubulointerstitial recruitment of human CD141hi CLEC9A+ and CD1c+ myeloid dendritic cell subsets in renal fibrosis and chronic kidney disease
Formatted title
Increased tubulointerstitial recruitment of human CD141hi CLEC9A+ and CD1c+ myeloid dendritic cell subsets in renal fibrosis and chronic kidney disease
Journal name American Journal of Physiology - Renal Physiology   Check publisher's open access policy
ISSN 0363-6127
1522-1466
Publication date 2013-11
Year available 2013
Sub-type Article (original research)
DOI 10.1152/ajprenal.00318.2013
Open Access Status DOI
Volume 305
Issue 10
Start page F1391
End page F1401
Total pages 11
Place of publication Bethesda, United States
Publisher American Physiological Society
Collection year 2014
Language eng
Formatted abstract
Dendritic cells (DCs) play critical roles in immune-mediated kidney diseases. Little is known, however, about DC subsets in human chronic kidney disease, with previous studies restricted to a limited set of pathologies and to using immunohistochemical methods. In this study, we developed novel protocols for extracting renal DC subsets from diseased human kidneys and identified, enumerated, and phenotyped them by multicolor flow cytometry. We detected significantly greater numbers of total DCs as well as CD141hi and CD1c+ myeloid DC (mDCs) subsets in diseased biopsies with interstitial fibrosis than diseased biopsies without fibrosis or healthy kidney tissue. In contrast, plasmacytoid DC numbers were significantly higher in the fibrotic group compared with healthy tissue only. Numbers of all DC subsets correlated with loss of kidney function, recorded as estimated glomerular filtration rate. CD141hi DCs expressed C-type lectin domain family 9 member A (CLEC9A), whereas the majority of CD1c+ DCs lacked the expression of CD1a and DC-specific ICAM-3-grabbing nonintegrin (DC-SIGN), suggesting these mDC subsets may be circulating CD141hi and CD1c+ blood DCs infiltrating kidney tissue. Our analysis revealed CLEC9A+ and CD1c+ cells were restricted to the tubulointerstitium. Notably, DC expression of the costimulatory and maturation molecule CD86 was significantly increased in both diseased cohorts compared with healthy tissue. Transforming growth factor-β levels in dissociated tissue supernatants were significantly elevated in diseased biopsies with fibrosis compared with nonfibrotic biopsies, with mDCs identified as a major source of this profibrotic cytokine. Collectively, our data indicate that activated mDC subsets, likely recruited into the tubulointerstitium, are positioned to play a role in the development of fibrosis and, thus, progression to chronic kidney disease.
Keyword Chronic kidney disease
Human dendritic cells
Interstitial fibrosis
Transforming growth factor-β
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2014 Collection
School of Medicine Publications
 
Versions
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 11 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 11 times in Scopus Article | Citations
Google Scholar Search Google Scholar
Created: Tue, 03 Dec 2013, 00:38:43 EST by System User on behalf of School of Medicine