Intracerebral Dendritic Cells Critically Modulate Encephalitogenic versus Regulatory Immune Responses in the CNS
| Autor: | Zsuzsanna Fabry, Alla L. Zozulya, Sonja Ortler, Christian Weidenfeller, Matyas Sandor, Heinz Wiendl, JangEun Lee |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
CD4-Positive T-Lymphocytes
Central Nervous System Lipopolysaccharides Encephalomyelitis Autoimmune Experimental Time Factors T-Lymphocytes Encephalomyelitis Freund's Adjuvant Inflammation Biology Article Myelin oligodendrocyte glycoprotein Immune System Phenomena Interferon-gamma Mice Immune system medicine Animals Picrotoxin Neuroinflammation Glycoproteins Interleukin-7 General Neuroscience Experimental autoimmune encephalomyelitis Interferon-alpha Forkhead Transcription Factors Dendritic Cells Mycobacterium tuberculosis Flow Cytometry medicine.disease Peptide Fragments Mice Inbred C57BL Disease Models Animal Interleukin 10 Freund's adjuvant Immunology biology.protein Central Nervous System Stimulants Female Myelin-Oligodendrocyte Glycoprotein medicine.symptom |
| Zdroj: | The Journal of Neuroscience. 29:140-152 |
| ISSN: | 1529-2401 0270-6474 |
| DOI: | 10.1523/jneurosci.2199-08.2009 |
| Popis: | Dendritic cells (DCs) appear in higher numbers within the CNS as a consequence of inflammation associated with autoimmune disorders, such as multiple sclerosis, but the contribution of these cells to the outcome of disease is not yet clear. Here, we show that stimulatory or tolerogenic functional states of intracerebral DCs regulate the systemic activation of neuroantigen-specific T cells, the recruitment of these cells into the CNS and the onset and progression of experimental autoimmune encephalomyelitis (EAE). Intracerebral microinjection of stimulatory DCs exacerbated the onset and clinical course of EAE, accompanied with an early T-cell infiltration and a decreased proportion of regulatory FoxP3-expressing cells in the brain. In contrast, the intracerebral microinjection of DCs modified by tumor necrosis factor α induced their tolerogenic functional state and delayed or prevented EAE onset. This triggered the generation of interleukin 10 (IL-10)-producing neuroantigen-specific lymphocytes in the periphery and restricted IL-17 production in the CNS. Our findings suggest that DCs are a rate-limiting factor for neuroinflammation. |
| Databáze: | OpenAIRE |
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