Centre for Immunobiology, Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, Scotland, UK.
Mucosal Immunol. 2013 May;6(3):498-510. doi: 10.1038/mi.2012.89. Epub 2012 Sep 19.
Macrophages (mφ) are essential for intestinal homeostasis and the pathology of inflammatory bowel disease (IBD), but it is unclear whether discrete mφ populations carry out these distinct functions or if resident mφ change during inflammation. We show here that most resident mφ in resting mouse colon express very high levels of CX3CR1, are avidly phagocytic and MHCII(hi), but are resistant to Toll-like receptor (TLR) stimulation, produce interleukin 10 constitutively, and express CD163 and CD206. A smaller population of CX3CR1(int) cells is present in resting colon and it expands during experimental colitis. Ly6C(hi)CCR2(+) monocytes can give rise to all mφ subsets in both healthy and inflamed colon and we show that the CX3CR1(int) pool represents a continuum in which newly arrived, recently divided monocytes develop into resident CX3CR1(hi) mφ. This process is arrested during experimental colitis, resulting in the accumulation of TLR-responsive pro-inflammatory mφ. Phenotypic analysis of human intestinal mφ indicates that analogous processes occur in the normal and Crohn's disease ileum. These studies show for the first time that resident and inflammatory mφ in the intestine represent alternative differentiation outcomes of the same precursor and targeting these events could offer routes for therapeutic intervention in IBD.
巨噬细胞（mφ）对于肠道内稳态和炎症性肠病（IBD）的病理学至关重要，但尚不清楚是否存在不同的 mφ 群体来执行这些不同的功能，或者在炎症过程中是否存在驻留 mφ 的变化。我们在这里表明，在静止状态下的小鼠结肠中，大多数驻留 mφ 表达高水平的 CX3CR1，具有强烈的吞噬作用和 MHCII（高），但对 Toll 样受体（TLR）刺激具有抗性，持续产生白细胞介素 10，并表达 CD163 和 CD206。在静止的结肠中存在一小部分 CX3CR1（int）细胞，在实验性结肠炎期间其数量增加。Ly6C（hi）CCR2（+）单核细胞可以在健康和炎症结肠中产生所有 mφ 亚群，我们表明 CX3CR1（int）池代表一个连续体，其中新到达的、最近分裂的单核细胞发育成驻留的 CX3CR1（hi）mφ。这个过程在实验性结肠炎期间被阻断，导致 TLR 反应性促炎 mφ 的积累。对人类肠道 mφ 的表型分析表明，在正常和克罗恩病回肠中也发生类似的过程。这些研究首次表明，肠道中的驻留和炎症 mφ 代表同一前体细胞的不同分化结果，针对这些事件可能为 IBD 的治疗干预提供途径。
