Neuropilin-1 Expression on CD4 T Cells Is Atherogenic and Facilitates T Cell Migration to the Aorta in Atherosclerosis.

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  • Author(s): Gaddis DE;Gaddis DE; Padgett LE; Padgett LE; Wu R; Wu R; Hedrick CC; Hedrick CC
  • Source:
    Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2019 Dec 15; Vol. 203 (12), pp. 3237-3246. Date of Electronic Publication: 2019 Nov 18.
  • Publication Type:
    Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
  • Language:
    English
  • Additional Information
    • Source:
      Publisher: American Association of Immunologists Country of Publication: United States NLM ID: 2985117R Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1550-6606 (Electronic) Linking ISSN: 00221767 NLM ISO Abbreviation: J Immunol Subsets: MEDLINE
    • Publication Information:
      Publication: Bethesda, MD : American Association of Immunologists
      Original Publication: Baltimore : Williams & Wilkins, c1950-
    • Subject Terms:
      Gene Expression*; Aorta/*metabolism ; Atherosclerosis/*etiology ; Atherosclerosis/*metabolism ; CD4-Positive T-Lymphocytes/*immunology ; CD4-Positive T-Lymphocytes/*metabolism ; Neuropilin-1/*genetics; Animals ; Aorta/pathology ; Atherosclerosis/pathology ; Biomarkers ; Cell Movement ; Cells, Cultured ; Humans ; Immunologic Memory ; Immunophenotyping ; Lipoproteins, LDL/metabolism ; Lymphocyte Activation/immunology ; Mice ; Neuropilin-1/metabolism
    • Abstract:
      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 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.
      (Copyright © 2019 by The American Association of Immunologists, Inc.)
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    • Grant Information:
      S10 RR027366 United States RR NCRR NIH HHS; P01 HL136275 United States HL NHLBI NIH HHS; R01 HL112276 United States HL NHLBI NIH HHS; P01 HL055798 United States HL NHLBI NIH HHS; T32 AI125179 United States AI NIAID NIH HHS
    • Accession Number:
      0 (Biomarkers)
      0 (Lipoproteins, LDL)
      0 (oxidized low density lipoprotein)
      144713-63-3 (Neuropilin-1)
    • Publication Date:
      Date Created: 20191120 Date Completed: 20200526 Latest Revision: 20220716
    • Publication Date:
      20221213
    • Accession Number:
      PMC8041247
    • Accession Number:
      10.4049/jimmunol.1900245
    • Accession Number:
      31740486