Macrophages Promote Atherosclerosis Development by Inhibiting CD8T Cell Apoptosis

Mediators Inflamm. 2024 Sep 21:2024:1929766. doi: 10.1155/2024/1929766. eCollection 2024.

Abstract

Background: Atherosclerosis is an inflammatory cardiovascular disease. However, whether the association of immune cells in plaques promotes the progression of this disease has not yet been completely elucidated.

Materials and methods: Thus, this study aimed to investigate the relationship between C1q+ macrophages and CD8T cells through scRNA-seq data reanalysis, quantitative real-time PCR, and flow cytometry. Chromatin immunoprecipitation-quantitative polymerase chain reaction, western blot, and antibody-blocking experiments were performed to investigate the role of macrophage-CD8T interaction in atherosclerosis. An atherosclerotic mouse model was developed to confirm our findings.

Results: Mechanistically, Spi1 expression induced by granulocyte-macrophage colony-stimulating factor promoted C1q expression in the macrophages. Moreover, C1q+ macrophages suppressed CD8T cell apoptosis by upregulating Slc7a7 expression to enhance the L-arginine uptake of CD8T cells. CD8T-derived interferon-γ promoted macrophage activation to induce atherosclerosis. Blockade of the C1q-C1qbp axis attenuated atherosclerosis.

Conclusion: In conclusion, macrophages interacting with CD8T promote atherosclerosis development via the C1q-C1qbp axis.

MeSH terms

  • Animals
  • Apoptosis*
  • Atherosclerosis* / metabolism
  • CD8-Positive T-Lymphocytes* / metabolism
  • Complement C1q / metabolism
  • Flow Cytometry
  • Granulocyte-Macrophage Colony-Stimulating Factor / metabolism
  • Interferon-gamma / metabolism
  • Macrophages* / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL*
  • Proto-Oncogene Proteins
  • Trans-Activators

Substances

  • Complement C1q
  • Granulocyte-Macrophage Colony-Stimulating Factor
  • Interferon-gamma
  • proto-oncogene protein Spi-1
  • Proto-Oncogene Proteins
  • Trans-Activators