Endothelial Cell-Derived Soluble CD200 Determines the Ability of Immune Cells to Cross the Blood-Brain Barrier.

Item request has been placed! ×
Item request cannot be made. ×
loading   Processing Request
Read More Add to Saved list
  • Additional Information
    • Source:
      Publisher: MDPI Country of Publication: Switzerland NLM ID: 101092791 Publication Model: Electronic Cited Medium: Internet ISSN: 1422-0067 (Electronic) Linking ISSN: 14220067 NLM ISO Abbreviation: Int J Mol Sci Subsets: MEDLINE
    • Publication Information:
      Original Publication: Basel, Switzerland : MDPI, [2000-
    • Subject Terms:
      Blood-Brain Barrier*/metabolism ; Blood-Brain Barrier*/immunology ; Antigens, CD*/metabolism ; Antigens, CD*/genetics ; Endothelial Cells*/metabolism ; Endothelial Cells*/immunology ; Cell Adhesion* ; T-Lymphocytes*/immunology ; T-Lymphocytes*/metabolism; Animals ; Mice ; Encephalomyelitis, Autoimmune, Experimental/immunology ; Encephalomyelitis, Autoimmune, Experimental/metabolism ; Encephalomyelitis, Autoimmune, Experimental/pathology ; Mice, Inbred C57BL ; Humans ; Brain/metabolism ; Brain/immunology
    • Abstract:
      The infiltration of immune cells into the central nervous system mediates the development of autoimmune neuroinflammatory diseases. We previously showed that the loss of either Fabp5 or calnexin causes resistance to the induction of experimental autoimmune encephalomyelitis (EAE) in mice, an animal model of multiple sclerosis (MS). Here we show that brain endothelial cells lacking either Fabp5 or calnexin have an increased abundance of cell surface CD200 and soluble CD200 (sCD200) as well as decreased T-cell adhesion. In a tissue culture model of the blood-brain barrier, antagonizing the interaction of CD200 and sCD200 with T-cell CD200 receptor (CD200R1) via anti-CD200 blocking antibodies or the RNAi-mediated inhibition of CD200 production by endothelial cells increased T-cell adhesion and transmigration across monolayers of endothelial cells. Our findings demonstrate that sCD200 produced by brain endothelial cells regulates immune cell trafficking through the blood-brain barrier and is primarily responsible for preventing activated T-cells from entering the brain.
    • References:
      Semin Cell Dev Biol. 2015 May;41:79-89. (PMID: 25534658)
      J Biol Chem. 2010 Jun 11;285(24):18928-38. (PMID: 20400506)
      Neuron. 2024 Jun 7;:. (PMID: 38889714)
      Immunity. 2000 Aug;13(2):233-42. (PMID: 10981966)
      Curr Opin Investig Drugs. 2005 May;6(5):483-8. (PMID: 15912961)
      Nucleic Acids Res. 2010 Oct;38(19):6684-96. (PMID: 20558599)
      FASEB J. 2020 Dec;34(12):16662-16675. (PMID: 33124722)
      PLoS One. 2013 Dec 12;8(12):e80490. (PMID: 24349001)
      J Neurosci. 2017 Jan 25;37(4):972-985. (PMID: 28123029)
      Eur J Immunol. 2022 Jun;52(6):869-881. (PMID: 35476319)
      JCI Insight. 2018 Mar 8;3(5):. (PMID: 29515033)
      PLoS One. 2015 Feb 06;10(2):e0117215. (PMID: 25658745)
      Am J Pathol. 2002 Nov;161(5):1669-77. (PMID: 12414514)
      J Anat. 2009 Jan;214(1):183-95. (PMID: 19166481)
      BMC Immunol. 2015 May 12;16:28. (PMID: 25962726)
      Nat Rev Immunol. 2015 Sep 15;15(9):545-58. (PMID: 26250739)
      Biochem Biophys Res Commun. 2017 Nov 4;493(1):202-206. (PMID: 28911862)
      Front Neurosci. 2019 Aug 07;13:840. (PMID: 31440137)
      Mediators Inflamm. 2021 May 31;2021:9999146. (PMID: 34158806)
      J Cell Mol Med. 2024 Mar;28(5):e17703. (PMID: 36876733)
      Oncotarget. 2023 Feb 04;14:96-103. (PMID: 36738455)
      Cells. 2023 Jan 24;12(3):. (PMID: 36766745)
      Handb Clin Neurol. 2014;122:173-89. (PMID: 24507518)
      Lancet Neurol. 2024 Jan;23(1):95-109. (PMID: 38101906)
      Vasc Biol. 2020 Mar 20;2(1):H1-H18. (PMID: 32923970)
      Cells. 2022 Mar 21;11(6):. (PMID: 35326506)
      PLoS One. 2016 Apr 25;11(4):e0152073. (PMID: 27111430)
      Am J Pathol. 2007 May;170(5):1695-712. (PMID: 17456775)
      Cell. 1990 Aug 10;62(3):435-45. (PMID: 2379237)
      J Immunol. 2009 Jun 15;182(12):7625-33. (PMID: 19494286)
      Molecules. 2015 Jul 28;20(8):13689-704. (PMID: 26225950)
      J Neurosci. 2010 Feb 10;30(6):2025-38. (PMID: 20147531)
      Front Cell Neurosci. 2017 May 04;11:129. (PMID: 28522962)
      J Clin Invest. 2022 Nov 1;132(21):. (PMID: 36074574)
      Br J Pharmacol. 2011 Oct;164(4):1079-106. (PMID: 21371012)
    • Grant Information:
      PS 168843 Canadian Institutes of Health Reserch
    • Contributed Indexing:
      Keywords: CD200; CD200R1; brain endothelial cells; calnexin; fatty acid binding protein 5; neurodegenerative diseases; sCD200
    • Accession Number:
      0 (Antigens, CD)
      UQ4V77A8VA (antigens, CD200)
    • Publication Date:
      Date Created: 20240914 Date Completed: 20240914 Latest Revision: 20240924
    • Publication Date:
      20240924
    • Accession Number:
      PMC11395061
    • Accession Number:
      10.3390/ijms25179262
    • Accession Number:
      39273210