Induction of inhibitory central nervous system-derived and stimulatory blood-derived dendritic cells suggests a dual role for granulocyte-macrophage colony-stimulating factor in central nervous system inflammation
| Autor: | Tobias Suter, Walter Reith, Lysann Hesske, Mathias Heikenwalder, Adriano Fontana, Marco Prinz, Christine Vincenzetti |
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| Přispěvatelé: | University of Zurich, Suter, T |
| Rok vydání: | 2010 |
| Předmět: |
GM
Chemokine T-Lymphocytes Encephalomyelitis ddc:616.07 10263 Institute of Experimental Immunology Lymphocyte Activation Monocytes Mice T-Lymphocytes/physiology Brain/ immunology/metabolism/pathology Cells Cultured Mice Knockout Mice Inbred BALB C CD11b Antigen biology Experimental autoimmune encephalomyelitis Brain Membrane Proteins/genetics/metabolism Chemokines/metabolism autoimmune encephalitis 2728 Neurology (clinical) Granulocyte macrophage colony-stimulating factor medicine.anatomical_structure Spinal Cord Dendritic Cells/ immunology/metabolism Spinal Cord/ immunology/metabolism/pathology Female Chemokines medicine.symptom medicine.drug Encephalomyelitis Autoimmune Experimental T cell 10208 Institute of Neuropathology Encephalomyelitis Autoimmune Experimental/ immunology/metabolism/pathology 610 Medicine & health CSF Inflammation Granulocyte-Macrophage Colony-Stimulating Factor/ metabolism Antigens CD11b/metabolism Antigens Differentiation/metabolism medicine central nervous system Animals Cell Proliferation fms-Like Tyrosine Kinase 3/metabolism Follicular dendritic cells Monocytes/ metabolism Granulocyte-Macrophage Colony-Stimulating Factor Membrane Proteins Dendritic Cells Dendritic cell medicine.disease Antigens Differentiation Mice Inbred C57BL fms-Like Tyrosine Kinase 3 Immunology 10033 Clinic for Immunology biology.protein 570 Life sciences Neurology (clinical) dendritic cells |
| Zdroj: | Brain, Vol. 133, No Pt 6 (2010) pp. 1637-1654 |
| ISSN: | 1460-2156 0006-8950 |
| DOI: | 10.1093/brain/awq081 |
| Popis: | The mononuclear phagocyte system, particularly dendritic cells, plays several pivotal roles in the development of multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis. Here, we demonstrate that functionally distinct dendritic cell subpopulations are present in the central nervous system during experimental autoimmune encephalomyelitis. At peak experimental autoimmune encephalomyelitis, the majority of dendritic cells consisted of a CD11b(+)F4/80(+) inflammatory dendritic cell subtype. Both granulocyte-macrophage colony-stimulating factor and chemokine (C-C motif) ligand 2 were previously suggested to recruit 'inflammatory' monocyte-derived dendritic cells to the central nervous system during experimental autoimmune encephalomyelitis. We show that intra-cerebral production of granulocyte-macrophage colony-stimulating factor leading to chemokine (C-C motif) ligand 2 induction and attraction of chemokine (C-C motif) receptor 2-positive precursors suffices to recruit dendritic cell populations identical to those observed in experimental autoimmune encephalomyelitis into the central nervous system of healthy mice. This does not occur with fms-like tyrosine kinase-3-ligand treatment. Both during experimental autoimmune encephalomyelitis and upon intra-cerebral granulocyte-macrophage colony-stimulating factor production, all myeloid dendritic cells, lymphoid dendritic cells and periphery-derived inflammatory dendritic cells stimulated T cell proliferation, whereas inflammatory dendritic cells that differentiated from central nervous system precursors inhibited T cell activation and pro-inflammatory cytokine production. Despite the capacity of granulocyte-macrophage colony-stimulating factor to induce central nervous system-derived inhibitory inflammatory dendritic cells, the administration of granulocyte-macrophage colony-stimulating factor into mice with experimental autoimmune encephalomyelitis resulted in exacerbated disease. Granulocyte-macrophage colony-stimulating factor thus has a dual role in the central nervous system: it directs both central nervous system-derived dendritic cells towards an inhibitory phenotype and recruits peripheral dendritic cells exhibiting pro-inflammatory functions. |
| Databáze: | OpenAIRE |
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