Macrophages driven to a novel state of activation have anti-inflammatory properties in mice
Macrophages driven to a novel state of activation have anti-inflammatory properties in mice
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DOI：
10.4049/jimmunol.180.1.335
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发表时间：
2008-01-01
影响因子：
4.4
通讯作者：
Geissler, Edward K.
中科院分区：
文献类型：
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作者：
Brem-Exner, Beate G.;Sattler, Christine;Geissler, Edward K.
炎症的反复发作是许多病理学的基础，特别是炎性肠病。在这项研究中，我们描述了一种新的激活状态的巨噬细胞群，这种激活状态可以减轻小鼠结肠炎。负责这种效应的细胞称为IFN-γ刺激的单核细胞衍生细胞（IFN γ-MdC），来源于小鼠脾、血液和骨髓单核细胞，并通过生成模式、细胞表面表型和功能与已知的巨噬细胞群区分开来。只有在表达CD 40 L的CD 4（+）T细胞、M-CSF和IFN-γ存在的情况下培养巨噬细胞时，才会出现IFN-γ-MdC。γ-MdC表达包括F4/80、CD 11b/c、CD 86和CD 274的标记物;它们对CD 4、CD 8、Gr 1、CD 19、CD 80和CD 207是阴性的。在功能上，IFN γ-MdC通过其富集共培养的T细胞群中的CD 4（+）CD 25（+）Foxp 3（+）调节细胞的能力来定义;这种富集，构成高达60%或更多的残留淋巴细胞，归因于扩增，但也归因于活化T细胞的细胞接触和半胱天冬酶依赖性耗竭。在小鼠中，IFN γ-MdC通过静脉内运输至肠道相关外周淋巴组织，包括肠系膜淋巴结、派伊尔集合淋巴结和结肠粘膜，并促进慢性结肠炎的临床和组织学消退。我们得出结论，IFN γ-MdC代表处于新的活化状态的巨噬细胞，具有多种T细胞抑制作用，具有治疗自身免疫性炎症的治疗潜力。
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.