Abstract
| Original language | English |
|---|---|
| Pages (from-to) | 1628 - 1638 |
| Number of pages | 11 |
| Journal | Journal of Immunology |
| Volume | 194 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - 2015 |
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CX3CR1 reduces kidney fibrosis by inhibiting local proliferation of profibrotic macrophages. / Engel, Daniel Robert; Krause, Torsten A; Snelgrove, Sarah Louise; Thiebes, Stephanie; Hickey, Michael John; Boor, Peter; Kitching, Arthur Richard; Kurts, Christian.
In: Journal of Immunology, Vol. 194, No. 4, 2015, p. 1628 - 1638.Research output: Contribution to journal › Article › Research › peer-review
TY - JOUR
T1 - CX3CR1 reduces kidney fibrosis by inhibiting local proliferation of profibrotic macrophages
AU - Engel, Daniel Robert
AU - Krause, Torsten A
AU - Snelgrove, Sarah Louise
AU - Thiebes, Stephanie
AU - Hickey, Michael John
AU - Boor, Peter
AU - Kitching, Arthur Richard
AU - Kurts, Christian
PY - 2015
Y1 - 2015
N2 - A dense network of macrophages and dendritic cells (DC) expressing the chemokine receptor CX3CR1 populates most tissues. We recently reported that CX3CR1 regulates the abundance of CD11c(+) DC in the kidney and thereby promotes renal inflammation in glomerulonephritis. Given that chronic inflammation usually causes fibrosis, we hypothesized that CX3CR1 deficiency should attenuate renal fibrosis. However, when we tested this hypothesis using the DC-independent murine fibrosis model of unilateral ureteral obstruction, kidney fibrosis was unexpectedly more severe, despite less intrarenal inflammation. Two-photon imaging and flow cytometry revealed in kidneys of CX3CR1-deficient mice more motile Ly6C/Gr-1(+) macrophages. Flow cytometry verified that renal macrophages were more abundant in the absence of CX3CR1 and produced more of the key profibrotic mediator, TGF-beta. Macrophages accumulated because of higher intrarenal proliferation, despite reduced monocyte recruitment and higher signs of apoptosis within the kidney. These findings support the theory that tissue macrophage numbers are regulated through local proliferation and identify CX3CR1 as a regulator of such proliferation. Thus, CX3CR1 inhibition should be avoided in DC-independent inflammatory diseases because it may promote fibrosis.
AB - A dense network of macrophages and dendritic cells (DC) expressing the chemokine receptor CX3CR1 populates most tissues. We recently reported that CX3CR1 regulates the abundance of CD11c(+) DC in the kidney and thereby promotes renal inflammation in glomerulonephritis. Given that chronic inflammation usually causes fibrosis, we hypothesized that CX3CR1 deficiency should attenuate renal fibrosis. However, when we tested this hypothesis using the DC-independent murine fibrosis model of unilateral ureteral obstruction, kidney fibrosis was unexpectedly more severe, despite less intrarenal inflammation. Two-photon imaging and flow cytometry revealed in kidneys of CX3CR1-deficient mice more motile Ly6C/Gr-1(+) macrophages. Flow cytometry verified that renal macrophages were more abundant in the absence of CX3CR1 and produced more of the key profibrotic mediator, TGF-beta. Macrophages accumulated because of higher intrarenal proliferation, despite reduced monocyte recruitment and higher signs of apoptosis within the kidney. These findings support the theory that tissue macrophage numbers are regulated through local proliferation and identify CX3CR1 as a regulator of such proliferation. Thus, CX3CR1 inhibition should be avoided in DC-independent inflammatory diseases because it may promote fibrosis.
UR - http://www.jimmunol.org/content/194/4/1628.full.pdf+html
U2 - 10.4049/jimmunol.1402149
DO - 10.4049/jimmunol.1402149
M3 - Article
VL - 194
SP - 1628
EP - 1638
JO - Journal of Immunology
JF - Journal of Immunology
SN - 0022-1767
IS - 4
ER -