Abstract
In antineutrophil cytoplasmic antibody-associated vasculitis (AAV), Toll-like receptors (TLRs) may be engaged by infection-associated patterns and by endogenous danger signals, linking infection and innate inflammation with this autoimmune disease. This study examined intrarenal TLR2, TLR4, and TLR9 expression and renal injury in AAV, testing the hypothesis that increased TLR expression correlates with renal injury. Patients with AAV exhibited both glomerular and tubulointerstitial expression of TLR2, TLR4, and TLR9, with TLR4 being the most prominent in both compartments. Glomerular TLR4 expression correlated with glomerular segmental necrosis and cellular crescents, with TLR2 expression correlating with glomerular segmental necrosis. The extent and intensity of glomerular and tubulointerstitial TLR4 expression and the intensity of glomerular TLR2 expression inversely correlated with the presenting estimated glomerular filtration rate. Although myeloid cells within the kidney expressed TLR2, TLR4, and TLR9, TLR2 and TLR4 colocalized with endothelial cells and podocytes, whereas TLR9 was expressed predominantly by podocytes. The functional relevance of intrarenal TLR expression was further supported by the colocalization of TLRs with their endogenous ligands high-mobility group box 1 and fibrinogen. Therefore, in AAV, the extent of intrarenal TLR4 and TLR2 expression and their correlation with renal injury indicates that TLR4, and to a lesser degree TLR2, may be potential therapeutic targets in this disease.
| Original language | English |
|---|---|
| Pages (from-to) | F1283-F1294 |
| Number of pages | 12 |
| Journal | American Journal of Physiology - Renal Physiology |
| Volume | 315 |
| Issue number | 5 |
| DOIs | |
| Publication status | Published - 1 Nov 2018 |
Keywords
- Antibodies
- Antineutrophil cytoplasmic
- Autoimmunity
- Glomerulonephritis
- Toll-like receptors
- Vasculitis
Cite this
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Intrarenal toll-like receptor 4 and toll-like receptor 2 expression correlates with injury in antineutrophil cytoplasmic antibody-associated vasculitis. / O’sullivan, Kim M.; Ford, Sharon L.; Longano, Anthony; Kitching, A. Richard; Holdsworth, Stephen R.
In: American Journal of Physiology - Renal Physiology, Vol. 315, No. 5, 01.11.2018, p. F1283-F1294.Research output: Contribution to journal › Article › Research › peer-review
TY - JOUR
T1 - Intrarenal toll-like receptor 4 and toll-like receptor 2 expression correlates with injury in antineutrophil cytoplasmic antibody-associated vasculitis
AU - O’sullivan, Kim M.
AU - Ford, Sharon L.
AU - Longano, Anthony
AU - Kitching, A. Richard
AU - Holdsworth, Stephen R.
PY - 2018/11/1
Y1 - 2018/11/1
N2 - In antineutrophil cytoplasmic antibody-associated vasculitis (AAV), Toll-like receptors (TLRs) may be engaged by infection-associated patterns and by endogenous danger signals, linking infection and innate inflammation with this autoimmune disease. This study examined intrarenal TLR2, TLR4, and TLR9 expression and renal injury in AAV, testing the hypothesis that increased TLR expression correlates with renal injury. Patients with AAV exhibited both glomerular and tubulointerstitial expression of TLR2, TLR4, and TLR9, with TLR4 being the most prominent in both compartments. Glomerular TLR4 expression correlated with glomerular segmental necrosis and cellular crescents, with TLR2 expression correlating with glomerular segmental necrosis. The extent and intensity of glomerular and tubulointerstitial TLR4 expression and the intensity of glomerular TLR2 expression inversely correlated with the presenting estimated glomerular filtration rate. Although myeloid cells within the kidney expressed TLR2, TLR4, and TLR9, TLR2 and TLR4 colocalized with endothelial cells and podocytes, whereas TLR9 was expressed predominantly by podocytes. The functional relevance of intrarenal TLR expression was further supported by the colocalization of TLRs with their endogenous ligands high-mobility group box 1 and fibrinogen. Therefore, in AAV, the extent of intrarenal TLR4 and TLR2 expression and their correlation with renal injury indicates that TLR4, and to a lesser degree TLR2, may be potential therapeutic targets in this disease.
AB - In antineutrophil cytoplasmic antibody-associated vasculitis (AAV), Toll-like receptors (TLRs) may be engaged by infection-associated patterns and by endogenous danger signals, linking infection and innate inflammation with this autoimmune disease. This study examined intrarenal TLR2, TLR4, and TLR9 expression and renal injury in AAV, testing the hypothesis that increased TLR expression correlates with renal injury. Patients with AAV exhibited both glomerular and tubulointerstitial expression of TLR2, TLR4, and TLR9, with TLR4 being the most prominent in both compartments. Glomerular TLR4 expression correlated with glomerular segmental necrosis and cellular crescents, with TLR2 expression correlating with glomerular segmental necrosis. The extent and intensity of glomerular and tubulointerstitial TLR4 expression and the intensity of glomerular TLR2 expression inversely correlated with the presenting estimated glomerular filtration rate. Although myeloid cells within the kidney expressed TLR2, TLR4, and TLR9, TLR2 and TLR4 colocalized with endothelial cells and podocytes, whereas TLR9 was expressed predominantly by podocytes. The functional relevance of intrarenal TLR expression was further supported by the colocalization of TLRs with their endogenous ligands high-mobility group box 1 and fibrinogen. Therefore, in AAV, the extent of intrarenal TLR4 and TLR2 expression and their correlation with renal injury indicates that TLR4, and to a lesser degree TLR2, may be potential therapeutic targets in this disease.
KW - Antibodies
KW - Antineutrophil cytoplasmic
KW - Autoimmunity
KW - Glomerulonephritis
KW - Toll-like receptors
KW - Vasculitis
UR - http://www.scopus.com/inward/record.url?scp=85055543988&partnerID=8YFLogxK
U2 - 10.1152/ajprenal.00040.2018
DO - 10.1152/ajprenal.00040.2018
M3 - Article
VL - 315
SP - F1283-F1294
JO - American Journal of Physiology - Renal Physiology
JF - American Journal of Physiology - Renal Physiology
SN - 1522-1466
IS - 5
ER -