| First Author | Gaddis DE | Year | 2019 |
| Journal | J Immunol | Volume | 203 |
| Issue | 12 | Pages | 3237-3246 |
| PubMed ID | 31740486 | Mgi Jnum | J:282219 |
| Mgi Id | MGI:6379925 | Doi | 10.4049/jimmunol.1900245 |
| Citation | Gaddis DE, et al. (2019) Neuropilin-1 Expression on CD4 T Cells Is Atherogenic and Facilitates T Cell Migration to the Aorta in Atherosclerosis. J Immunol 203(12):3237-3246 |
| abstractText | Neuropilin 1 (Nrp1) is a type I transmembrane protein that plays important roles in axonal guidance, neuronal development, and angiogenesis. Nrp1 also helps migrate thymus-derived regulatory T cells to vascular endothelial growth factor (VEGF)-producing tumors. However, little is known about the role of Nrp1 on CD4 T cells in atherosclerosis. In ApoE(-/-) mice fed a Western diet for 15 wk, we found a 2-fold increase in Nrp1(+)Foxp3(-) CD4 T cells in their spleens, periaortic lymph nodes, and aortas, compared with chow-fed mice. Nrp1(+)Foxp3(-) CD4 T cells had higher proliferation potential, expressed higher levels of the memory marker CD44, and produced more IFN-gamma when compared with Nrp1(-) CD4 T cells. Treatment of CD4 T cells with oxLDL increased Nrp1 expression. Furthermore, atherosclerosis-susceptible mice selectively deficient for Nrp1 expression on T cells developed less atherosclerosis than their Nrp1-sufficient counterparts. Mechanistically, we found that CD4 T cells that express Nrp1 have an increased capacity to migrate to the aorta and periaortic lymph nodes compared to Nrp1(-) T cells, suggesting that the expression of Nrp1 facilitates the recruitment of CD4 T cells into the aorta where they can be pathogenic. Thus, we have identified a novel role of Nrp1 on CD4 T cells in atherosclerosis. These results suggest that manipulation of Nrp1 expression on T cells can affect the outcome of atherosclerosis and lower disease incidence. |
