Abstract
The anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitides are autoimmune diseases associated with significant morbidity and mortality. They often affect the kidney causing rapidly progressive glomerulonephritis. While signalling by complement anaphylatoxin C5a though the C5a receptor is important in this disease, the role of the anaphylatoxin C3a signalling via the C3a receptor (C3aR) is not known. Using two different murine models of anti-myeloperoxidase (MPO) glomerulonephritis, one mediated by passive transfer of anti-MPO antibodies, the other by cell-mediated immunity, we found that the C3aR did not alter histological disease severity. However, it promoted macrophage recruitment to the inflamed glomerulus and inhibited the generation of MPO-ANCA whilst not influencing T cell autoimmunity. Thus, whilst the C3aR modulates some elements of disease pathogenesis, overall it is not critical in effector responses and glomerular injury caused by autoimmunity to MPO.
| Original language | English |
|---|---|
| Article number | e0190655 |
| Number of pages | 15 |
| Journal | PLoS ONE |
| Volume | 13 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - 1 Jan 2018 |
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The C3aR promotes macrophage infiltration and regulates anca production but does not affect glomerular injury in experimental antimyeloperoxidase glomerulonephritis. / Dick, Jonathan; Gan, Poh Yi; Richard Kitching, A.; Holdsworth, Stephen R.
In: PLoS ONE, Vol. 13, No. 1, e0190655, 01.01.2018.Research output: Contribution to journal › Article › Research › peer-review
TY - JOUR
T1 - The C3aR promotes macrophage infiltration and regulates anca production but does not affect glomerular injury in experimental antimyeloperoxidase glomerulonephritis
AU - Dick, Jonathan
AU - Gan, Poh Yi
AU - Richard Kitching, A.
AU - Holdsworth, Stephen R.
PY - 2018/1/1
Y1 - 2018/1/1
N2 - The anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitides are autoimmune diseases associated with significant morbidity and mortality. They often affect the kidney causing rapidly progressive glomerulonephritis. While signalling by complement anaphylatoxin C5a though the C5a receptor is important in this disease, the role of the anaphylatoxin C3a signalling via the C3a receptor (C3aR) is not known. Using two different murine models of anti-myeloperoxidase (MPO) glomerulonephritis, one mediated by passive transfer of anti-MPO antibodies, the other by cell-mediated immunity, we found that the C3aR did not alter histological disease severity. However, it promoted macrophage recruitment to the inflamed glomerulus and inhibited the generation of MPO-ANCA whilst not influencing T cell autoimmunity. Thus, whilst the C3aR modulates some elements of disease pathogenesis, overall it is not critical in effector responses and glomerular injury caused by autoimmunity to MPO.
AB - The anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitides are autoimmune diseases associated with significant morbidity and mortality. They often affect the kidney causing rapidly progressive glomerulonephritis. While signalling by complement anaphylatoxin C5a though the C5a receptor is important in this disease, the role of the anaphylatoxin C3a signalling via the C3a receptor (C3aR) is not known. Using two different murine models of anti-myeloperoxidase (MPO) glomerulonephritis, one mediated by passive transfer of anti-MPO antibodies, the other by cell-mediated immunity, we found that the C3aR did not alter histological disease severity. However, it promoted macrophage recruitment to the inflamed glomerulus and inhibited the generation of MPO-ANCA whilst not influencing T cell autoimmunity. Thus, whilst the C3aR modulates some elements of disease pathogenesis, overall it is not critical in effector responses and glomerular injury caused by autoimmunity to MPO.
UR - http://www.scopus.com/inward/record.url?scp=85040338972&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0190655
DO - 10.1371/journal.pone.0190655
M3 - Article
VL - 13
JO - PLoS ONE
JF - PLoS ONE
SN - 1932-6203
IS - 1
M1 - e0190655
ER -