IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v15y2024i1d10.1038_s41467-024-50540-5.html
   My bibliography  Save this article

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
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-024-50540-5
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/s41467-024-50540-5?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Yingdi Wang & Masanori Nakayama & Mara E. Pitulescu & Tim S. Schmidt & Magdalena L. Bochenek & Akira Sakakibara & Susanne Adams & Alice Davy & Urban Deutsch & Urs Lüthi & Alcide Barberis & Laura E. Be, 2010. "Ephrin-B2 controls VEGF-induced angiogenesis and lymphangiogenesis," Nature, Nature, vol. 465(7297), pages 483-486, May.
    2. Paulus Mrass & Sreenivasa Rao Oruganti & G. Matthew Fricke & Justyna Tafoya & Janie R. Byrum & Lihua Yang & Samantha L. Hamilton & Mark J. Miller & Melanie E. Moses & Judy L. Cannon, 2017. "ROCK regulates the intermittent mode of interstitial T cell migration in inflamed lungs," Nature Communications, Nature, vol. 8(1), pages 1-14, December.
    3. Leon Hosang & Roger Cugota Canals & Felicia Joy Flier & Jacqueline Hollensteiner & Rolf Daniel & Alexander Flügel & Francesca Odoardi, 2022. "The lung microbiome regulates brain autoimmunity," Nature, Nature, vol. 603(7899), pages 138-144, March.
    4. Astrid Gillich & Fan Zhang & Colleen G. Farmer & Kyle J. Travaglini & Serena Y. Tan & Mingxia Gu & Bin Zhou & Jeffrey A. Feinstein & Mark A. Krasnow & Ross J. Metzger, 2020. "Capillary cell-type specialization in the alveolus," Nature, Nature, vol. 586(7831), pages 785-789, October.
    5. Irinna Papangeli & Jongmin Kim & Inna Maier & Saejeong Park & Aram Lee & Yujung Kang & Keiichiro Tanaka & Omar F. Khan & Hyekyung Ju & Yoko Kojima & Kristy Red-Horse & Daniel G. Anderson & Arndt F. Si, 2016. "MicroRNA 139-5p coordinates APLNR-CXCR4 crosstalk during vascular maturation," Nature Communications, Nature, vol. 7(1), pages 1-11, September.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Rida Al-Rifai & Marie Vandestienne & Jean-Rémi Lavillegrand & Tristan Mirault & Julie Cornebise & Johanne Poisson & Ludivine Laurans & Bruno Esposito & Chloé James & Olivier Mansier & Pierre Hirsch & , 2022. "JAK2V617F mutation drives vascular resident macrophages toward a pathogenic phenotype and promotes dissecting aortic aneurysm," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    2. Eun-A Kwak & Christopher C. Pan & Aaron Ramonett & Sanjay Kumar & Paola Cruz-Flores & Tasmia Ahmed & Hannah R. Ortiz & Jeffrey J. Lochhead & Nathan A. Ellis & Ghassan Mouneimne & Teodora G. Georgieva , 2022. "βIV-spectrin as a stalk cell-intrinsic regulator of VEGF signaling," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    3. Ahmed A. Raslan & Tho X. Pham & Jisu Lee & Konstantinos Kontodimas & Andrew Tilston-Lunel & Jillian Schmottlach & Jeongmin Hong & Taha Dinc & Andreea M. Bujor & Nunzia Caporarello & Aude Thiriot & Ulr, 2024. "Lung injury-induced activated endothelial cell states persist in aging-associated progressive fibrosis," Nature Communications, Nature, vol. 15(1), pages 1-20, December.
    4. Christina M. Termini & Amara Pang & Tiancheng Fang & Martina Roos & Vivian Y. Chang & Yurun Zhang & Nicollette J. Setiawan & Lia Signaevskaia & Michelle Li & Mindy M. Kim & Orel Tabibi & Paulina K. Li, 2021. "Neuropilin 1 regulates bone marrow vascular regeneration and hematopoietic reconstitution," Nature Communications, Nature, vol. 12(1), pages 1-17, December.
    5. Fuchun Yang & Shiva Kalantari & Banzhan Ruan & Shaogang Sun & Zhaoqun Bian & Jun-Lin Guan, 2023. "Autophagy inhibition prevents lymphatic malformation progression to lymphangiosarcoma by decreasing osteopontin and Stat3 signaling," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    6. Guolun Wang & Bingqiang Wen & Zicheng Deng & Yufang Zhang & Olena A. Kolesnichenko & Vladimir Ustiyan & Arun Pradhan & Tanya V. Kalin & Vladimir V. Kalinichenko, 2022. "Endothelial progenitor cells stimulate neonatal lung angiogenesis through FOXF1-mediated activation of BMP9/ACVRL1 signaling," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    7. Kevin Boyé & Luiz Henrique Geraldo & Jessica Furtado & Laurence Pibouin-Fragner & Mathilde Poulet & Doyeun Kim & Bryce Nelson & Yunling Xu & Laurent Jacob & Nawal Maissa & Dritan Agalliu & Lena Claess, 2022. "Endothelial Unc5B controls blood-brain barrier integrity," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    8. Shujuan Zhao & Kedous Y. Mekbib & Martijn A. Ent & Garrett Allington & Andrew Prendergast & Jocelyn E. Chau & Hannah Smith & John Shohfi & Jack Ocken & Daniel Duran & Charuta G. Furey & Le Thi Hao & P, 2023. "Mutation of key signaling regulators of cerebrovascular development in vein of Galen malformations," Nature Communications, Nature, vol. 14(1), pages 1-23, December.
    9. Jonas Stewen & Kai Kruse & Anca T. Godoi-Filip & Zenia & Hyun-Woo Jeong & Susanne Adams & Frank Berkenfeld & Martin Stehling & Kristy Red-Horse & Ralf H. Adams & Mara E. Pitulescu, 2024. "Eph-ephrin signaling couples endothelial cell sorting and arterial specification," Nature Communications, Nature, vol. 15(1), pages 1-23, December.
    10. Gan Zhao & Maria E. Gentile & Lulu Xue & Christopher V. Cosgriff & Aaron I. Weiner & Stephanie Adams-Tzivelekidis & Joanna Wong & Xinyuan Li & Sara Kass-Gergi & Nicolas P. Holcomb & Maria C. Basal & K, 2024. "Vascular endothelial-derived SPARCL1 exacerbates viral pneumonia through pro-inflammatory macrophage activation," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    11. Kuo-Sheng Hsu & James M. Dunleavey & Christopher Szot & Liping Yang & Mary Beth Hilton & Karen Morris & Steven Seaman & Yang Feng & Emily M. Lutz & Robert Koogle & Francesco Tomassoni-Ardori & Saurabh, 2022. "Cancer cell survival depends on collagen uptake into tumor-associated stroma," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    12. Massimiliano Bissa & Sohyoung Kim & Veronica Galli & Slim Fourati & Sarkis Sarkis & Anush Arakelyan & Isabela Silva Castro & Mohammad Arif Rahman & Saori Fujiwara & Monica Vaccari & Jeffrey A. Tomalka, 2023. "HIV vaccine candidate efficacy in female macaques mediated by cAMP-dependent efferocytosis and V2-specific ADCC," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    13. Sandra Schrenk & Lindsay J. Bischoff & Jillian Goines & Yuqi Cai & Shruti Vemaraju & Yoshinobu Odaka & Samantha R. Good & Joseph S. Palumbo & Sara Szabo & Damien Reynaud & Catherine D. Raamsdonk & Ric, 2023. "MEK inhibition reduced vascular tumor growth and coagulopathy in a mouse model with hyperactive GNAQ," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    14. Hongyu Liu & Ran Duan & Xiaoyu He & Jincu Qi & Tianming Xing & Yahan Wu & Liping Zhou & Lingling Wang & Yujing Shao & Fulei Zhang & Huixing Zhou & Xingdong Gu & Bowen Lin & Yuanyuan Liu & Yan Wang & Y, 2023. "Endothelial deletion of PTBP1 disrupts ventricular chamber development," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    15. Wiebke Sachs & Lukas Blume & Desiree Loreth & Lisa Schebsdat & Favian Hatje & Sybille Koehler & Uta Wedekind & Marlies Sachs & Stephanie Zieliniski & Johannes Brand & Christian Conze & Bogdan I. Flore, 2024. "The proteasome modulates endocytosis specifically in glomerular cells to promote kidney filtration," Nature Communications, Nature, vol. 15(1), pages 1-21, December.
    16. Nunzia Caporarello & Jisu Lee & Tho X. Pham & Dakota L. Jones & Jiazhen Guan & Patrick A. Link & Jeffrey A. Meridew & Grace Marden & Takashi Yamashita & Collin A. Osborne & Aditya V. Bhagwate & Steven, 2022. "Dysfunctional ERG signaling drives pulmonary vascular aging and persistent fibrosis," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
    17. Mehmet Can Uçar & Edouard Hannezo & Emmi Tiilikainen & Inam Liaqat & Emma Jakobsson & Harri Nurmi & Kari Vaahtomeri, 2023. "Self-organized and directed branching results in optimal coverage in developing dermal lymphatic networks," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    18. Jing Huang & Weijun Huang & Junzhe Yi & Yiwen Deng & Ruijie Li & Jieying Chen & Jiahao Shi & Yuan Qiu & Tao Wang & Xiaoyong Chen & Xiaoran Zhang & Andy Peng Xiang, 2023. "Mesenchymal stromal cells alleviate depressive and anxiety-like behaviors via a lung vagal-to-brain axis in male mice," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    19. M. Gabriele Bixel & Kishor K. Sivaraj & Melanie Timmen & Vishal Mohanakrishnan & Anusha Aravamudhan & Susanne Adams & Bong-Ihn Koh & Hyun-Woo Jeong & Kai Kruse & Richard Stange & Ralf H. Adams, 2024. "Angiogenesis is uncoupled from osteogenesis during calvarial bone regeneration," Nature Communications, Nature, vol. 15(1), pages 1-22, December.
    20. Sarasa Isobe & Ramesh V. Nair & Helen Y. Kang & Lingli Wang & Jan-Renier Moonen & Tsutomu Shinohara & Aiqin Cao & Shalina Taylor & Shoichiro Otsuki & David P. Marciano & Rebecca L. Harper & Mir S. Adi, 2023. "Reduced FOXF1 links unrepaired DNA damage to pulmonary arterial hypertension," Nature Communications, Nature, vol. 14(1), pages 1-18, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-50540-5. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.