Macrophages driven to a novel state of activation have anti-inflammatory properties in mice
| Autor: | Christian U. Blank, Fred Fändrich, Christine Sattler, Seiichiro Inoue, Beate G. Brem-Exner, Hans J. Schlitt, Stuart J. Knechtle, Edward K. Geissler, Katharina Kronenberg, Gudrun E. Koehl, Stefan Farkas, James A. Hutchinson |
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| Rok vydání: | 2007 |
| Předmět: |
Cell Survival
T cell Immunology chemical and pharmacologic phenomena Inflammation Biology T-Lymphocytes Regulatory Monocytes Autoimmune Diseases Interferon-gamma Mice medicine Immunology and Allergy Macrophage Animals Mesentery IL-2 receptor Lymphocytes CD40 Antigens Receptors Interferon CD86 Mice Inbred BALB C Macrophages Interleukin-2 Receptor alpha Subunit FOXP3 Forkhead Transcription Factors Macrophage Activation Colitis Coculture Techniques medicine.anatomical_structure Caspases CD4 Antigens Chronic Disease Female Lymph Nodes medicine.symptom CD80 CD8 |
| Zdroj: | Journal of immunology (Baltimore, Md. : 1950). 180(1) |
| ISSN: | 0022-1767 |
| Popis: | Recurrent episodes of inflammation underlie numerous pathologies, notably those of inflammatory bowel diseases. In this study, we describe a population of macrophages in a novel state of activation that mitigates colitis in mice. The cells responsible for this effect, called IFN-γ-stimulated monocyte-derived cells (IFNγ-MdC), derive from mouse spleen, blood, and bone marrow monocytes and are distinguished from known macrophage populations by mode of generation, cell surface phenotype, and function. IFNγ-MdC only arise when macrophages are cultivated in the presence of CD40L-expressing CD4+ T cells, M-CSF, and IFN-γ. IFNγ-MdC express markers including F4/80, CD11b/c, CD86, and CD274; they are negative for CD4, CD8, Gr1, CD19, CD80, and CD207. Functionally, IFNγ-MdC are defined by their capacity to enrich cocultured T cell populations for CD4+CD25+Foxp3+ regulatory cells; this enrichment, constituting up to 60% or more of residual lymphocytes, is attributed to an expansion, but also to a cell contact and caspase-dependent depletion of activated T cells. In mice, IFNγ-MdC delivered i.v. traffic to gut-associated peripheral lymphoid tissues, including the mesenteric lymph nodes, Peyer’s patches, and colonic mucosa, and promote the clinical and histological resolution of chronic colitis. We conclude that IFNγ-MdC represent macrophages in a novel state of activation, possessing multiple T cell-suppressive effects with therapeutic potential for the treatment of autoimmune inflammation. |
| Databáze: | OpenAIRE |
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