Expression of the chemokine receptor CCR6 in human renal inflammation

TY - JOUR

T1 - Expression of the chemokine receptor CCR6 in human renal inflammation

AU - Welsh-Bacic, Desa

AU - Lindenmeyer, Maja

AU - Cohen, Clemens D

AU - Draganovici, Dan

AU - Mandelbaum, Jana

AU - Edenhofer, Ilka

AU - Ziegler, Urs

AU - Regele, Heinz

AU - Wüthrich, Rudolf P

AU - Segerer, Stephan

PY - 2011/4

Y1 - 2011/4

N2 - 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.

AB - 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.

KW - Adolescent

KW - Adult

KW - Aged

KW - Aged, 80 and over

KW - Case-Control Studies

KW - Chemokine CCL20

KW - Child

KW - Child, Preschool

KW - Female

KW - Fluorescent Antibody Technique

KW - Glomerulonephritis

KW - Glomerulonephritis, IGA

KW - Humans

KW - Immunoenzyme Techniques

KW - Infant

KW - Infant, Newborn

KW - Inflammation

KW - Kidney Failure, Chronic

KW - Male

KW - Middle Aged

KW - Nephritis, Interstitial

KW - RNA, Messenger

KW - Receptors, CCR6

KW - Reverse Transcriptase Polymerase Chain Reaction

KW - Young Adult

KW - Comparative Study

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1093/ndt/gfq560

DO - 10.1093/ndt/gfq560

M3 - SCORING: Journal article

C2 - 20844183

VL - 26

SP - 1211

EP - 1220

JO - NEPHROL DIAL TRANSPL

JF - NEPHROL DIAL TRANSPL

SN - 0931-0509

IS - 4

ER -