Macrophages driven to a novel state of activation have anti-inflammatory properties in mice

被引:64
作者
Brem-Exner, Beate G. [1 ,3 ]
Sattler, Christine [1 ]
Hutchinson, James A. [3 ]
Koehl, Gudrun E. [1 ]
Kronenberg, Katharina [1 ]
Farkas, Stefan [1 ]
Inoue, Seiichiro [1 ]
Blank, Christian [2 ]
Knechtle, Stuart J. [4 ]
Schlitt, Hans J. [1 ]
Faendrich, Fred [3 ]
Geissler, Edward K. [1 ]
机构
[1] Univ Regensburg, Dept Surg, D-93053 Regensburg, Germany
[2] Univ Regensburg, Dept Hematol & Oncol, D-93053 Regensburg, Germany
[3] Univ Hosp, Dept Gen & Thorac Surg, Kiel, Germany
[4] Univ Wisconsin Sch Med & Publ Hlth, Div Organ Transplantat, Dept Surg, Madison, WI 53705 USA
关键词
D O I
10.4049/jimmunol.180.1.335
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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.
引用
收藏
页码:335 / 349
页数:15
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