Τίτλος:
Mannan-MOG35-55 Reverses Experimental Autoimmune Encephalomyelitis, Inducing a Peripheral Type 2 Myeloid Response, Reducing CNS Inflammation, and Preserving Axons in Spinal Cord Lesions
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
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.
Συγγραφείς:
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.
Περιοδικό:
Frontiers in Immunology
Εκδότης:
Frontiers Media S.A
Λέξεις-κλειδιά:
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
DOI:
10.3389/fimmu.2020.575451
