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Scavenger Receptor A Mediates the Clearance and Immunological Screening of MDA-Modified Antigen by M2-Type

Andreas Warnecke1, Sonja Abele1, Sravani Musunuri2

  • 1Applied Immunology and Immunotherapy, Department of Clinical Neuroscience, Karolinska Institutet, Center for Molecular Medicine, Karolinska University Hospital at Solna, 17176, Stockholm, Sweden.

Neuromolecular Medicine
|August 23, 2017
PubMed

Insights

Malondialdehyde (MDA)-modified myelin oligodendrocyte glycoprotein (MOG) is rapidly cleared by macrophages via SRA, promoting T cell responses without worsening CNS autoimmunity in models. MDA adducts act as clearance signals for phagocytes.

Area of Science:

  • Neuroimmunology
  • Lipid Peroxidation
  • Autoimmunity

Background:

  • Myelin oligodendrocyte glycoprotein (MOG) is a key autoantigen in CNS autoimmunity.
  • Lipid peroxidation can modify proteins, potentially altering their immunogenicity.
  • Understanding antigen processing and presentation is crucial for autoimmune disease research.

Purpose of the Study:

  • To investigate the uptake of malondialdehyde (MDA)-modified MOG by macrophages.
  • To identify the receptor responsible for MDA-modified MOG uptake.
  • To determine the immunomodulatory effects of MDA-modified MOG in CNS autoimmunity.

Main Methods:

  • Utilized custom fluorescently labeled MOG and MDA-modified MOG.
  • Quantified uptake by macrophage populations using flow cytometry.
  • Identified scavenger receptor A (SRA) as the primary uptake receptor.
  • Assessed T cell proliferation and EAE disease course in vivo.

Main Results:

  • SRA-mediated uptake of MDA-modified MOG was tenfold more efficient than native MOG.
  • Uptake was predominantly by anti-inflammatory M2-type macrophages.
  • MDA-modified MOG enhanced MOG-specific T cell recall proliferation in vitro.
  • MDA modification did not exacerbate EAE but induced antibodies to MOG and MDA adducts.

Conclusions:

  • MDA adducts act as clearance signals, facilitating rapid antigen removal by phagocytes.
  • This rapid uptake and processing by antigen-presenting cells (APCs) enhances T cell stimulation.
  • MDA modification of MOG promotes antigen clearance and immunological screening without increasing disease severity in EAE models.
Keywords:
AutoimmunityMOG-EAEMacrophagesMalondialdeydePosttranslational modificationsScavenger receptors

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