Mannan-MOG35-55 Reverses Experimental Autoimmune Encephalomyelitis, Inducing a Peripheral Type 2 Myeloid Response, Reducing CNS Inflammation, and Preserving Axons in Spinal Cord Lesions
| Autor: | Maria Evangelidou, Vivian Tseveleki, Ioannis Kanistras, Fotis Lampros, Hans Lassmann, Anastasia Dagkonaki, Maria-Eleni Androutsou, Irini Papazian, Theodore Tselios, Torben Ruhwedel, Lise T. Jensen, Maria Anagnostouli, Maria Avloniti, Lesley Probert, John Matsoukas, Wiebke Möbius |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Male Myeloid T-Lymphocytes multiple sclerosis Lymphocyte Activation Immune tolerance Myelin 0302 clinical medicine immune system diseases Immunology and Allergy Medicine M2 macrophages antigen-specific immunotherapy Myeloid Cells Cells Cultured Original Research biology Greece Experimental autoimmune encephalomyelitis Middle Aged medicine.anatomical_structure Spinal Cord neuroprotection Female Immunosuppressive Agents lcsh:Immunologic diseases. Allergy PD-L1 Adult Encephalomyelitis Autoimmune Experimental Synaptosomal-Associated Protein 25 CNS demyelination T cell Immunology Mice Transgenic Neuroprotection Myelin oligodendrocyte glycoprotein MOGAD 03 medical and health sciences Young Adult Ym1/Chi3l3 Animals Humans Cell Proliferation business.industry humanized DR2 mice Interleukin-2 Receptor alpha Subunit Myelin Basic Protein HLA-DR Antigens medicine.disease Axons nervous system diseases Mice Inbred C57BL 030104 developmental biology nervous system Gene Expression Regulation Case-Control Studies biology.protein Interleukin-2 business lcsh:RC581-607 030217 neurology & neurosurgery |
| Zdroj: | Frontiers in Immunology Dagkonaki, A, Avloniti, M, Evangelidou, M, Papazian, I, Kanistras, I, Tseveleki, V, Lampros, F, Tselios, T, Jensen, L T, Möbius, W, Ruhwedel, T, Androutsou, M E, Matsoukas, J, Anagnostouli, M, Lassmann, H & Probert, L 2020, ' Mannan-MOG35-55 Reverses Experimental Autoimmune Encephalomyelitis, Inducing a Peripheral Type 2 Myeloid Response, Reducing CNS Inflammation, and Preserving Axons in Spinal Cord Lesions ', Frontiers in Immunology, vol. 11, 575451 . https://doi.org/10.3389/fimmu.2020.575451 Frontiers in Immunology, Vol 11 (2020) |
| ISSN: | 1664-3224 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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