Expression of the chemokine receptor CCR6 in human renal inflammation.
BACKGROUND
Nodular inflammatory cell infiltrates with defined microarchitecture, i.e. tertiary lymphoid organs, develop in the tubulointerstitium during chronic renal inflammation. CCR6 and the corresponding ligand CCL20 are involved in the formation of gut-associated lymphatic tissue. We hypothesized that CCR6 might be involved in the formation of nodular infiltrates in the kidney.


METHODS
CCR6- and CD20-positive B cells were localized in renal biopsies with IgA nephropathy (n = 13), membranous nephropathy (n = 12), crescentic glomerulonephritis (cGN, n = 11) and chronic interstitial nephritis (n = 13), and in pre-implantation biopsies as controls (n = 8). The mRNA expression of CCR6 and the ligand CCL20 was quantified by real-time RT-PCR in 51 renal biopsies of the same disease entities.


RESULTS
In the pre-transplant biopsies, CCR6 was expressed by endothelial cells of peritubular and glomerular capillaries. In patients with glomerulonephritis, infiltrating cells were positive particularly in areas of nodular inflammatory cell accumulations. A major part of the CCR6-positive cells were CD20-positive B cells, but a part of the CD3-positive T cells were also found to be positive. The constitutive expression of CCR6 on the endothelium of glomerular capillaries was lost in biopsies with progressive injury. Tubular epithelial cells expressed CCR6 in inflamed kidneys, most commonly on the basolateral side.


CONCLUSIONS
CCR6 and the corresponding ligand CCL20 might therefore be involved in the recruitment of T and B cells to organized nodular infiltrates in chronic renal inflammation. The functional role of endothelial CCR6 needs to be evaluated in further studies.
Welsh-Bacic
Desa
D
Division of Nephrology, University Hospital, Zurich, Switzerland.
Lindenmeyer
Maja
M
Cohen
Clemens D
CD
Draganovici
Dan
D
Mandelbaum
Jana
J
Edenhofer
Ilka
I
Ziegler
Urs
U
Regele
Heinz
H
Wüthrich
Rudolf P
RP
Segerer
Stephan
S
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D054418:Chemokine CCL20 / Q000235:genetics / Q000378:metabolism*; D002648:Child; D002675:Child, Preschool; D005260:Female; D005455:Fluorescent Antibody Technique; D005921:Glomerulonephritis / Q000378:metabolism*; D005922:Glomerulonephritis, IGA / Q000378:metabolism*; D006801:Humans; D007124:Immunoenzyme Techniques; D007223:Infant; D007231:Infant, Newborn; D007249:Inflammation / Q000378:metabolism*; D007676:Kidney Failure, Chronic / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009395:Nephritis, Interstitial / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D054399:Receptors, CCR6 / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055815:Young Adult
C108355:CCL20 protein, human; C106311:CCR6 protein, human; D054418:Chemokine CCL20; D012333:RNA, Messenger; D054399:Receptors, CCR6