TY - JOUR
TI - Mannan-MOG35-55 Reverses Experimental Autoimmune Encephalomyelitis, Inducing a Peripheral Type 2 Myeloid Response, Reducing CNS Inflammation, and Preserving Axons in Spinal Cord Lesions
AU - Dagkonaki, A.
AU - Avloniti, M.
AU - Evangelidou, M.
AU - Papazian, I.
AU - Kanistras, I.
AU - Tseveleki, V.
AU - Lampros, F.
AU - Tselios, T.
AU - Jensen, L.T.
AU - Möbius, W.
AU - Ruhwedel, T.
AU - Androutsou, M.-E.
AU - Matsoukas, J.
AU - Anagnostouli, M.
AU - Lassmann, H.
AU - Probert, L.
JO - Frontiers in Immunology
PY - 2020
VL - 11
TODO - null
SP - null
PB - Frontiers Media S.A
SN - null
TODO - 10.3389/fimmu.2020.575451
TODO - CD11b antigen;  cell marker;  chi3l3;  glycoprotein p 15095;  HLA DR antigen;  HLA DRB1 antigen;  interleukin 10;  interleukin 1beta;  interleukin 2;  major histocompatibility antigen class 2;  mannan;  mannan conjugated murine myelin oligodendrocyte glycoprotein peptide 35 55;  mannose receptor;  mbp13 32;  mbp83 99;  mog1 20;  mog35 55;  myelin;  myelin oligodendrocyte glycoprotein;  pertussis toxin;  phytohemagglutinin;  plp139 154;  plp178 191;  synaptosomal associated protein 25;  T lymphocyte receptor;  thymidine;  transcription factor FOXP3;  unclassified drug;  HLA DR antigen;  immunosuppressive agent;  interleukin 2;  interleukin 2 receptor alpha;  Mbp protein, mouse;  myelin basic protein;  Snap25 protein, mouse;  synaptosomal associated protein 25, allergic encephalomyelitis;  animal cell;  animal experiment;  animal model;  animal tissue;  antigen presenting cell;  Article;  axon;  blood sampling;  bone marrow cell;  CD4+ T lymphocyte;  cell infiltration;  cell isolation;  cell maturation;  cell proliferation;  cell stimulation;  cell vacuole;  cytokine production;  demyelination;  density gradient centrifugation;  DNA extraction;  draining lymph node;  electron microscopy;  Escherichia coli;  experimental autoimmune encephalomyelitis;  female;  flow cytometry;  gene expression;  genetic susceptibility;  genotype;  histopathology;  human;  human cell;  immune response;  immunization;  immunohistochemistry;  immunological tolerance;  in vitro study;  inflammation;  lymphocyte proliferation;  multiple sclerosis;  Mycobacterium tuberculosis;  nerve injury;  nervous system development;  nonhuman;  oligodendroglia;  peptide synthesis;  peripheral blood mononuclear cell;  protein expression;  real time polymerase chain reaction;  RNA extraction;  spinal cord injury;  spinal cord lesion;  spleen cell;  synaptosome;  transgenic mouse;  tumor associated leukocyte;  adult;  animal;  axon;  bone marrow cell;  C57BL mouse;  case control study;  cell culture;  drug effect;  experimental autoimmune encephalomyelitis;  gene expression regulation;  genetics;  Greece;  immunology;  lymphocyte activation;  male;  metabolism;  middle aged;  pathology;  spinal cord;  T lymphocyte;  young adult, Adult;  Animals;  Axons;  Case-Control Studies;  Cell Proliferation;  Cells, Cultured;  Encephalomyelitis, Autoimmune, Experimental;  Female;  Gene Expression Regulation;  Greece;  HLA-DR Antigens;  Humans;  Immunosuppressive Agents;  Interleukin-2;  Interleukin-2 Receptor alpha Subunit;  Lymphocyte Activation;  Male;  Mice, Inbred C57BL;  Mice, Transgenic;  Middle Aged;  Myelin Basic Protein;  Myeloid Cells;  Spinal Cord;  Synaptosomal-Associated Protein 25;  T-Lymphocytes;  Young Adult
TODO - CNS autoantigens conjugated to oxidized mannan (OM) induce antigen-specific T cell tolerance and protect mice against autoimmune encephalomyelitis (EAE). To investigate whether OM-peptides treat EAE initiated by human MHC class II molecules, we administered OM-conjugated murine myelin oligodendrocyte glycoprotein peptide 35-55 (OM-MOG) to humanized HLA-DR2b transgenic mice (DR2b.Ab°), which are susceptible to MOG-EAE. OM-MOG protected DR2b.Ab° mice against MOG-EAE by both prophylactic and therapeutic applications. OM-MOG reversed clinical symptoms, reduced spinal cord inflammation, demyelination, and neuronal damage in DR2b.Ab° mice, while preserving axons within lesions and inducing the expression of genes associated with myelin (Mbp) and neuron (Snap25) recovery in B6 mice. OM-MOG-induced tolerance was peptide-specific, not affecting PLP178-191-induced EAE or polyclonal T cell proliferation responses. OM-MOG-induced immune tolerance involved rapid induction of PD-L1- and IL-10-producing myeloid cells, increased expression of Chi3l3 (Ym1) in secondary lymphoid organs and characteristics of anergy in MOG-specific CD4+ T cells. The results show that OM-MOG treats MOG-EAE in a peptide-specific manner, across mouse/human MHC class II barriers, through induction of a peripheral type 2 myeloid cell response and T cell anergy, and suggest that OM-peptides might be useful for suppressing antigen-specific CD4+ T cell responses in the context of human autoimmune CNS demyelination. © Copyright © 2020 Dagkonaki, Avloniti, Evangelidou, Papazian, Kanistras, Tseveleki, Lampros, Tselios, Jensen, Möbius, Ruhwedel, Androutsou, Matsoukas, Anagnostouli, Lassmann and Probert.
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