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Max Planck Institute for Molecular Biomedicine

Nat. Commun., Jul 25 2024, 15 (1) 6282 | https://doi.org/10.1038/s41467-024-50540-5 Apelin modulates inflammation and leukocyte recruitment in experimental autoimmune encephalomyelitis

Hongryeol Park¹, Jian Song², Hyun-Woo Jeong¹, Max L. B. Grönloh³, Bong Ihn Koh¹, Esther Bovay¹, Kee-Pyo Kim⁴, Luisa Klotz⁵, Patricia A. Thistlethwaite⁶, Jaap D. van Buul³, Lydia Sorokin² & Ralf H. Adams¹

¹Max Planck Institute for Molecular Biomedicine, Department of Tissue Morphogenesis, Münster, Germany.

²Institute of Physiological Chemistry and Pathobiochemistry and Cells-in-Motion Interfaculty Centre (CIMIC), University of Münster, Münster, Germany.

³Vascular Cell Biology Lab, Department of Medical Biochemistry, Amsterdam UMC, and Section Molecular Cytology at Swammerdam Institute for Life Sciences, Leeuwenhoek Centre for Advanced Microscopy, University of Amsterdam, Amsterdam, The Netherlands.

⁴Department of Medical Life Sciences, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.

⁵Department of Neurology, University of Münster, Münster, Germany.

⁶Division of Cardiothoracic Surgery, University of California, San Diego, CA, USA.

Corresponding authors

Correspondence to Hongryeol Park or Ralf H. Adams.

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.

논문정보

형식Research article
게재일2024년 07월 (BRIC 등록일 2024-07-29)
연구진국외 연구진
분야 생명과학 > 분자생물학

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