Expression of antigen processing and presenting molecules by Schwann cells in inflammatory neuropathies.
Schwann cells are the myelinating glia cells of the peripheral nervous system (PNS) and can become targets of an autoimmune response in inflammatory neuropathies like the Guillain-Barré syndrome (GBS). Professional antigen presenting cells (APCs) are known to promote autoimmune responses in target tissues by presenting self-antigens. Other cell types could participate in local autoimmune responses by acting as nonprofessional APCs. Using a combined approach of immunocytochemistry, immunohistochemistry, and flow cytometry analysis we demonstrate that human Schwann cells express the antigen processing and presenting machinery (APM) in vitro and in vivo. Moreover, cultured human Schwann cells increase the expression of proteasome subunit delta (Y), antigen peptide transporter TAP2, and HLA Class I and HLA Class II complexes in an inflammatory environment. In correlation with this observation, Schwann cells in sural nerve biopsies from GBS patients show increased expression of antigen processing and presenting molecules. Furthermore, cultured human Schwann cells can proteolytically digest fluorescently-labeled nonmammalian antigen ovalbumin. Taken together, our data suggest antigen processing and presentation as a possible function of Schwann cells that may contribute to (auto)immune responses within peripheral nerves.
Meyer Zu Horste
Gerd
G
Department of Neurology, Heinrich-Heine-University, Düsseldorf, Germany. gerd.mzh@uni-duesseldorf.de
Heidenreich
Holger
H
Lehmann
Helmar C
HC
Ferrone
Soldano
S
Hartung
Hans-Peter
HP
Wiendl
Heinz
H
Kieseier
Bernd C
BC
D000071450:ATP Binding Cassette Transporter, Subfamily B, Member 3; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism; D017951:Antigen Presentation / Q000276:immunology / Q000502:physiology*; D000938:Antigen-Presenting Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D002478:Cells, Cultured; D005434:Flow Cytometry / Q000379:methods; D005786:Gene Expression Regulation / Q000276:immunology*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D020275:Guillain-Barre Syndrome / Q000473:pathology*; D006680:HLA Antigens / Q000378:metabolism; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D006801:Humans; D007231:Infant, Newborn; D016898:Interferon-alpha / Q000494:pharmacology; D010047:Ovalbumin / Q000494:pharmacology; D046988:Proteasome Endopeptidase Complex; D020800:Receptor, Nerve Growth Factor / Q000378:metabolism; D009418:S100 Proteins / Q000378:metabolism; D012583:Schwann Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D013497:Sural Nerve / Q000473:pathology; D013997:Time Factors
D000071450:ATP Binding Cassette Transporter, Subfamily B, Member 3; D018528:ATP-Binding Cassette Transporters; D005904:Glial Fibrillary Acidic Protein; D006680:HLA Antigens; D015395:Histocompatibility Antigens Class I; D016898:Interferon-alpha; D020800:Receptor, Nerve Growth Factor; D009418:S100 Proteins; C071692:TAP2 protein, human; D010047:Ovalbumin; D046988:Proteasome Endopeptidase Complex