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Apelin modulates inflammation and leukocyte recruitment in experimental autoimmune encephalomyelitis

Author

Listed:
  • Hongryeol Park

    (Department of Tissue Morphogenesis)

  • Jian Song

    (University of Münster)

  • Hyun-Woo Jeong

    (Department of Tissue Morphogenesis)

  • Max L. B. Grönloh

    (University of Amsterdam)

  • Bong Ihn Koh

    (Department of Tissue Morphogenesis)

  • Esther Bovay

    (Department of Tissue Morphogenesis)

  • Kee-Pyo Kim

    (The Catholic University of Korea)

  • Luisa Klotz

    (University of Münster)

  • Patricia A. Thistlethwaite

    (University of California)

  • Jaap D. Buul

    (University of Amsterdam)

  • Lydia Sorokin

    (University of Münster)

  • Ralf H. Adams

    (Department of Tissue Morphogenesis)

Abstract

Demyelination due to autoreactive T cells and inflammation in the central nervous system are principal features of multiple sclerosis (MS), a chronic and highly disabling human disease affecting brain and spinal cord. Here, we show that treatment with apelin, a secreted peptide ligand for the G protein-coupled receptor APJ/Aplnr, is protective in experimental autoimmune encephalomyelitis (EAE), an animal model of MS. Apelin reduces immune cell entry into the brain, delays the onset and reduces the severity of EAE. Apelin affects the trafficking of leukocytes through the lung by modulating the expression of cell adhesion molecules that mediate leukocyte recruitment. In addition, apelin induces the internalization and desensitization of its receptor in endothelial cells (ECs). Accordingly, protection against EAE major outcomes of apelin treatment are phenocopied by loss of APJ/Aplnr function, achieved by EC-specific gene inactivation in mice or knockdown experiments in cultured primary endothelial cells. Our findings highlight the importance of the lung-brain axis in neuroinflammation and indicate that apelin targets the transendothelial migration of immune cells into the lung during acute inflammation.

Suggested Citation

  • Hongryeol Park & Jian Song & Hyun-Woo Jeong & Max L. B. Grönloh & Bong Ihn Koh & Esther Bovay & Kee-Pyo Kim & Luisa Klotz & Patricia A. Thistlethwaite & Jaap D. Buul & Lydia Sorokin & Ralf H. Adams, 2024. "Apelin modulates inflammation and leukocyte recruitment in experimental autoimmune encephalomyelitis," Nature Communications, Nature, vol. 15(1), pages 1-20, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-50540-5
    DOI: 10.1038/s41467-024-50540-5
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