TY - JOUR
T1 - Neuropilin-1 expression on CD4 T Cells is atherogenic and facilitates T Cell migration to the aorta in atherosclerosis
AU - Gaddis, Dalia E.
AU - Padgett, Lindsey E.
AU - Wu, Runpei
AU - Hedrick, Catherine C.
N1 - Funding Information:
This work was supported by the American Heart Association (13POST16990031 to D.E.G. and 19POST34450020 to L.E.P.), the American Diabetes Association (7-12-MN-13 to D.E.G. and C.C.H.), and the National Institutes of Health (P01 HL055798 and P01 HL136275 to C.C.H., R01 HL112276 to C.C.H., T32 AI125279-01 Training in Immunological Mechanisms Training Grant to L.E.P., and S10 RR027366-01A1 to the La Jolla Institute for Immunology Flow Cytometry Core Facility).
Publisher Copyright:
© 2019 by The American Association of Immunologists, Inc.
PY - 2019
Y1 - 2019
N2 - 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-γ when compared with Nrp12 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 Nrp12 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.
AB - 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-γ when compared with Nrp12 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 Nrp12 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.
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U2 - 10.4049/jimmunol.1900245
DO - 10.4049/jimmunol.1900245
M3 - Article
C2 - 31740486
AN - SCOPUS:85076332988
SN - 0022-1767
VL - 203
SP - 3237
EP - 3246
JO - Journal of Immunology
JF - Journal of Immunology
IS - 12
ER -