| First Author | Dong L | Year | 2016 |
| Journal | J Am Soc Nephrol | Volume | 27 |
| Issue | 6 | Pages | 1753-64 |
| PubMed ID | 26449606 | Mgi Jnum | J:290192 |
| Mgi Id | MGI:6437593 | Doi | 10.1681/ASN.2015050540 |
| Citation | Dong L, et al. (2016) T Cell CX3CR1 Mediates Excess Atherosclerotic Inflammation in Renal Impairment. J Am Soc Nephrol 27(6):1753-64 |
| abstractText | 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 TH17 cells were obtained from CX3CR1(-/-) splenocytes than from wild-type splenocytes after polarization with IL-6, IL-23, and TGFbeta Polarization of TH17 or TREG cells, or stimulation of splenocytes with TGFbeta alone, increased T cell CX3CR1 reporter gene expression. Furthermore, TGFbeta 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 TGFbeta and is instrumental in enhanced atherosclerosis in renal impairment. |
