In:
Journal of the American Society of Nephrology, Ovid Technologies (Wolters Kluwer Health), Vol. 27, No. 6 ( 2016-6), p. 1753-1764
Abstract:
Reduced kidney function increases the risk for atherosclerosis and cardiovascular death. Leukocytes in the arterial wall contribute to atherosclerotic plaque formation. We investigated the role of fractalkine receptor CX3CR1 in atherosclerotic inflammation in renal impairment. Apoe−/− (apolipoprotein E) CX3CR1−/− mice with renal impairment were protected from increased aortic atherosclerotic lesion size and macrophage accumulation. Deficiency of CX3CR1 in bone marrow, only, attenuated atherosclerosis in renal impairment in an independent atherosclerosis model of LDL receptor–deficient ( LDLr−/− ) mice as well. Analysis of inflammatory leukocytes in atherosclerotic mixed bone-marrow chimeric mice (50% wild-type/50% CX3CR1−/− bone marrow into LDLr−/− mice) showed that CX3CR1 cell intrinsically promoted aortic T cell accumulation much more than CD11b + CD11c + myeloid cell accumulation and increased IL-17-producing T cell counts. In vitro , fewer T H17 cells were obtained from CX3CR1−/− splenocytes than from wild-type splenocytes after polarization with IL-6, IL-23, and TGF β . Polarization of T H17 or T REG cells, or stimulation of splenocytes with TGF β alone, increased T cell CX3CR1 reporter gene expression. Furthermore, TGF β induced CX3CR1 mRNA expression in wild-type cells in a dose- and time-dependent manner. In atherosclerotic LDLr−/− mice, CX3CR1+/− T cells upregulated CX3CR1 and IL-17A production in renal impairment, whereas CX3CR1−/− T cells did not. Transfer of CX3CR1+/− but not Il17a−/− T cells into LDLr−/−CX3CR1−/− mice increased aortic lesion size and aortic CD11b + CD11c + myeloid cell accumulation in renal impairment. In summary, T cell CX3CR1 expression can be induced by TGF β and is instrumental in enhanced atherosclerosis in renal impairment.
Type of Medium:
Online Resource
ISSN:
1046-6673
,
1533-3450
DOI:
10.1681/ASN.2015050540
Language:
English
Publisher:
Ovid Technologies (Wolters Kluwer Health)
Publication Date:
2016
detail.hit.zdb_id:
2029124-3
Permalink