Medizinische Klinik und Poliklinik I, Klinikum der Universität, Ludwig-Maximilians-Universität and Deutsches Herzzentrum München, Technische Universität München, Munich, Germany.
Nat Immunol. 2013 Jan;14(1):41-51. doi: 10.1038/ni.2477. Epub 2012 Nov 25.
Coordinated navigation within tissues is essential for cells of the innate immune system to reach the sites of inflammatory processes, but the signals involved are incompletely understood. Here we demonstrate that NG2(+) pericytes controlled the pattern and efficacy of the interstitial migration of leukocytes in vivo. In response to inflammatory mediators, pericytes upregulated expression of the adhesion molecule ICAM-1 and released the chemoattractant MIF. Arteriolar and capillary pericytes attracted and interacted with myeloid leukocytes after extravasating from postcapillary venules, 'instructing' them with pattern-recognition and motility programs. Inhibition of MIF neutralized the migratory cues provided to myeloid leukocytes by NG2(+) pericytes. Hence, our results identify a previously unknown role for NG2(+) pericytes as an active component of innate immune responses, which supports the immunosurveillance and effector function of extravasated neutrophils and macrophages.
固有免疫系统的细胞在组织内进行协调导航对于到达炎症过程部位至关重要,但相关信号尚不完全清楚。在这里,我们证明 NG2(+)周细胞控制了白细胞在体内的间质迁移的模式和效率。在炎症介质的刺激下,周细胞上调了黏附分子 ICAM-1 的表达,并释放趋化因子 MIF。血管周细胞和毛细血管周细胞在从后微静脉渗出后吸引并与髓样白细胞相互作用,用模式识别和运动程序“指导”它们。抑制 MIF 中和了 NG2(+)周细胞向髓样白细胞提供的迁移线索。因此,我们的结果确定了 NG2(+)周细胞作为固有免疫反应的一个主动组成部分的先前未知作用,它支持渗出的中性粒细胞和巨噬细胞的免疫监视和效应功能。