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          Institute: MPI für Neurobiologie     Collection: Neuroimmunology     Display Documents

ID: 10140.0, MPI für Neurobiologie / Neuroimmunology
Fc receptors are critical for autoimmune inflammatory damage to the central nervous system in experimental autoimmune encephalomyelitis
Authors:Abdul-Majid, K. B.; Stefferl, Andreas; Bourquin, Carole; Lassmann, Hans; Linington, Christopher; Olsson, T.; Kleinau, S.; Harris, R. A.
Date of Publication (YYYY-MM-DD):2002-01
Title of Journal:Scandinavian Journal of Immunology
Journal Abbrev.:Scand. J. Immunol.
Issue / Number:1
Start Page:70
End Page:81
Review Status:Peer-review
Audience:Not Specified
Abstract / Description:Multiple sclerosis (MS) is simulated by various forms of experimental autoimmune encephalomyelitis, in which T cells, antibodies, cytokines and complementary factors interact with the central nervous system (CNS) myelin proteins and lead to inflammatory damage. We investigated the role of Fc receptors (FcRs), which link the cellular and humoral branches of the immune system, in myelin oligodendrocyte glycoprotein (MOG)- induced experimental autoimmune encephalomyelitis (EAE), using two different FcRgamma knockout DBA/1 mice. The first knockout were the FcRgamma chain-deficient mice, which lack FcgammaRI, FcgammaRIII and FcepsilonRI, while the second knockout mice lack only FcgammaRII. The lack of FcgammaRII enhanced the disease susceptibility with associated increased CNS demyelination. While FcRgamma(+/+) DBA/1 mice also developed pronounced CNS infiltration and myelin destruction, FcRgamma(- /-) littermates were protected despite initial peripheral autoimmune responses to MOG. In vitro analyses revealed equivalent potentials of fluid phase phagocytosis of myelin and MOG in bone-marrow macrophages derived from both FcRgamma(+/+) and FcRgamma(-/-) mice, while MOG-inimunoglobulin(Ig)G immune complexes were only internalized by FcRgamma(+/+) macrophages. This was associated with cellular activation in FcRgamma(+/+) but not FcRgamma(-/-) macrophages, as assessed by the activation of intracellular mitogen activated protein (MAP)- kinase signalling elements. We propose that protection from EAE in FcRgamma-deficient mice is due to the inefficient antigen processing/presentation of myelin proteins during the induction of secondary immune responses locally in the CNS, which leads to demyelination. This demonstrates the importance of FcR in the promotion of autoimmune inflammation of the CNS and highlights the therapeutic possibility of treatment of MS with FcR-directed modalities.
External Publication Status:published
Document Type:Article
Affiliations:MPI für Neurobiologie/Neuroimmunology (Wekerle)
External Affiliations:Karolinska Hosp, Ctr Mol Med L804, Neuroimmunol Unit, SE-17176; Stockholm, Sweden; Karolinska Hosp, Ctr Mol Med L804, Neuroimmunol Unit, SE-17176 Stockholm, Sweden; Univ Vienna, Inst Brain Res, A-1090 Vienna, Austria; Max Planck Inst Neurobiol, Dept Neuroimmunol, Martinsried, Germany; Uppsala Univ, Dept Genet & Pathol, SE-75185 Uppsala, Sweden
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