Brem-Exner, Beate G. and Sattler, Christine and Hutchinson, James A. and Koehl, Gudrun E. and Kronenberg, Katharina and Farkas, Stefan and Inoue, Seiichiro and Blank, Christian and Knechtle, Stuart J. and Schlitt, Hans J. and Faendrich, Fred and Geissler, Edward K. (2008) Macrophages driven to a novel state of activation have anti-inflammatory properties in mice. JOURNAL OF IMMUNOLOGY, 180 (1). pp. 335-349. ISSN 0022-1767,
Full text not available from this repository. (Request a copy)Abstract
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-gamma-stimulated monocyte-derived cells (IFN gamma-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. IFN gamma-MdC only arise when macrophages are cultivated in the presence of CD40L-expressing CD4(+) T cells, M-CSF, and IFN-gamma. IF gamma,-MdC express markers including F4/80, CD11b/c, CD86, and CD274; they are negative for CD4, CD8, Gr1, CD19, CD80, and CD207. Functionally, IFN gamma-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, IFN gamma-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 IFN gamma-MdC represent macrophages in a novel state of activation, possessing multiple T cell -suppressive effects with therapeutic potential for the treatment of autoimmune inflammation.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | SODIUM-INDUCED COLITIS; REGULATORY T-CELLS; POTENTIAL MECHANISM; PRESENTING CELLS; IFN-GAMMA; SCID MICE; APOPTOSIS; MONOCYTE; DISEASE; DEATH; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Chirurgie Medicine > Lehrstuhl für Innere Medizin III (Hämatologie und Internistische Onkologie) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 18 Nov 2020 07:21 |
| Last Modified: | 18 Nov 2020 07:21 |
| URI: | https://pred.uni-regensburg.de/id/eprint/31686 |
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