Chen Chih-Chiang, Wang Lei, Plikus Maksim V, Jiang Ting Xin, Murray Philip J, Ramos Raul, Guerrero-Juarez Christian F, Hughes Michael W, Lee Oscar K, Shi Songtao, Widelitz Randall B, Lander Arthur D, Chuong Cheng Ming
Department of Pathology, University of Southern California, Los Angeles, CA 90033, USA; Department of Dermatology, Taipei Veterans General Hospital, Taipei 112, Taiwan, ROC; Institute of Clinical Medicine and Department of Dermatology, National Yang-Ming University, Taipei, Taiwan 112, ROC.
State Key Laboratory of Military Stomatology, Department of Oral and Maxillofacial Surgery, School of Stomatology, The Fourth Military Medical University, Xi'an, Shaanxi 710032, China.
Cell. 2015 Apr 9;161(2):277-90. doi: 10.1016/j.cell.2015.02.016.
Coordinated organ behavior is crucial for an effective response to environmental stimuli. By studying regeneration of hair follicles in response to patterned hair plucking, we demonstrate that organ-level quorum sensing allows coordinated responses to skin injury. Plucking hair at different densities leads to a regeneration of up to five times more neighboring, unplucked resting hairs, indicating activation of a collective decision-making process. Through data modeling, the range of the quorum signal was estimated to be on the order of 1 mm, greater than expected for a diffusible molecular cue. Molecular and genetic analysis uncovered a two-step mechanism, where release of CCL2 from injured hairs leads to recruitment of TNF-α-secreting macrophages, which accumulate and signal to both plucked and unplucked follicles. By coupling immune response with regeneration, this mechanism allows skin to respond predictively to distress, disregarding mild injury, while meeting stronger injury with full-scale cooperative activation of stem cells.
协调的器官行为对于有效应对环境刺激至关重要。通过研究毛囊对有图案的拔毛的再生反应，我们证明器官水平的群体感应允许对皮肤损伤做出协调反应。以不同密度拔毛会导致多达五倍的相邻未拔的休止期毛发再生，这表明激活了一个集体决策过程。通过数据建模，群体信号的范围估计在1毫米左右，比可扩散分子信号预期的范围更大。分子和遗传分析揭示了一个两步机制，其中受损毛发释放CCL2会导致分泌TNF-α的巨噬细胞的募集，这些巨噬细胞聚集并向拔毛和未拔毛的毛囊发出信号。通过将免疫反应与再生相结合，这种机制使皮肤能够对损伤做出预测性反应，忽略轻度损伤，同时在遇到更严重损伤时通过干细胞的全面协同激活来应对。
