PMID- 24049150
OWN - NLM
STAT- MEDLINE
DCOM- 20140116
LR  - 20211203
IS  - 1522-1466 (Electronic)
IS  - 1522-1466 (Linking)
VI  - 305
IP  - 10
DP  - 2013 Nov 15
TI  - Increased tubulointerstitial recruitment of human CD141(hi) CLEC9A(+) and CD1c(+) 
      myeloid dendritic cell subsets in renal fibrosis and chronic kidney disease.
PG  - F1391-401
LID - 10.1152/ajprenal.00318.2013 [doi]
AB  - 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 CD141(hi) 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. CD141(hi) 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 CD141(hi) 
      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-beta 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.
FAU - Kassianos, Andrew J
AU  - Kassianos AJ
AD  - Conjoint Kidney Research Laboratory, Pathology Queensland, Queensland Institute 
      of Medical Research, Level 9, Bancroft Centre, Herston 4006, Queensland, 
      Australia. ray.wilkinson@qimr.edu.au.
FAU - Wang, Xiangju
AU  - Wang X
FAU - Sampangi, Sandeep
AU  - Sampangi S
FAU - Muczynski, Kimberly
AU  - Muczynski K
FAU - Healy, Helen
AU  - Healy H
FAU - Wilkinson, Ray
AU  - Wilkinson R
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130918
PL  - United States
TA  - Am J Physiol Renal Physiol
JT  - American journal of physiology. Renal physiology
JID - 100901990
RN  - 0 (Antigens, CD1)
RN  - 0 (Antigens, Surface)
RN  - 0 (Biomarkers)
RN  - 0 (CD1C protein, human)
RN  - 0 (CLEC9a protein, human)
RN  - 0 (Cytokines)
RN  - 0 (Glycoproteins)
RN  - 0 (Inflammation Mediators)
RN  - 0 (Lectins, C-Type)
RN  - 0 (Receptors, Mitogen)
RN  - 0 (THBD protein, human)
RN  - 0 (Thrombomodulin)
RN  - 0 (Transforming Growth Factor beta)
SB  - IM
MH  - Aged
MH  - Antigens, CD1/*analysis
MH  - Antigens, Surface/*analysis
MH  - Biomarkers/analysis
MH  - Biopsy
MH  - Case-Control Studies
MH  - Cell Count
MH  - *Chemotaxis
MH  - Cytokines/analysis
MH  - Dendritic Cells/*immunology
MH  - Disease Progression
MH  - Female
MH  - Fibrosis
MH  - Flow Cytometry
MH  - Glycoproteins/*analysis
MH  - Humans
MH  - Immunophenotyping
MH  - Inflammation Mediators/analysis
MH  - Kidney/*immunology/pathology
MH  - Lectins, C-Type/*analysis
MH  - Male
MH  - Middle Aged
MH  - Myeloid Cells/*immunology
MH  - Receptors, Mitogen/*analysis
MH  - Renal Insufficiency, Chronic/*immunology/pathology
MH  - Thrombomodulin
MH  - Transforming Growth Factor beta/analysis
OTO - NOTNLM
OT  - chronic kidney disease
OT  - human dendritic cells
OT  - interstitial fibrosis
OT  - transforming growth factor-beta
OT  - tubulointerstitium
EDAT- 2013/09/21 06:00
MHDA- 2014/01/17 06:00
CRDT- 2013/09/20 06:00
PHST- 2013/09/20 06:00 [entrez]
PHST- 2013/09/21 06:00 [pubmed]
PHST- 2014/01/17 06:00 [medline]
AID - ajprenal.00318.2013 [pii]
AID - 10.1152/ajprenal.00318.2013 [doi]
PST - ppublish
SO  - Am J Physiol Renal Physiol. 2013 Nov 15;305(10):F1391-401. doi: 
      10.1152/ajprenal.00318.2013. Epub 2013 Sep 18.