Inflammation triggers immediate rather than progressive changes in monocyte differentiation in the small intestine
Inflammation triggers immediate rather than progressive changes in monocyte differentiation in the small intestine
复制标题
DOI：
10.1038/s41467-019-11148-2
复制
发表时间：
2019-07-19
影响因子：
16.6
通讯作者：
Pabst, Oliver
中科院分区：
文献类型：
--
作者：
Desalegn, Girmay;Pabst, Oliver
骨髓来源的循环单核细胞有助于肠道巨噬细胞群体的补充和维持。肠道单核细胞经历环境依赖性表型和功能适应，以维持局部免疫平衡或支持肠道炎症。在这里，我们使用单核细胞过继转移来解剖正常和炎症小肠中单核细胞向巨噬细胞分化的动力学。我们发现，在稳态期间，CCR 2和β 7-整联蛋白介导单核细胞向肠道的组成性归巢。相比之下，肠道炎症通过CCR 2增加单核细胞募集，而不是β 7-整联蛋白。在非发炎的肠中，单核细胞逐渐分化以表达通常与致耐受性巨噬细胞功能相关的基因。相反，一旦进入发炎的肠道，单核细胞适应不同的表达模式，在一个部分Trem-1依赖的方式。我们的观察结果表明，炎症从根本上改变了组织中单核细胞分化的动力学和模式。
Bone marrow-derived circulating monocytes contribute to the replenishment and maintenance of the intestinal macrophage population. Intestinal monocytes undergo contextdependent phenotypic and functional adaptations to either maintain local immune balance or support intestinal inflammation. Here we use monocyte adoptive transfer to dissect the dynamics of monocyte-to-macrophage differentiation in normal and inflamed small intestine. We find that during homeostasis CCR2 and beta 7-integrin mediate constitutive homing of monocytes to the gut. By contrast, intestinal inflammation increases monocyte recruitment via CCR2, but not beta 7-integrin. In the non-inflamed intestine, monocytes gradually differentiate to express genes typically associated with tolerogenic macrophage functions. Conversely, immediately upon entry into the inflamed intestine, monocytes adapt a different expression pattern in a partly Trem-1-dependent manner. Our observations suggest that inflammation fundamentally changes the kinetics and modalities of monocyte differentiation in tissues.