Department of Comparative Biology and Experimental Medicine, Faculty of Veterinary Medicine, University of Calgary, Calgary, Alberta, Canada.
Schulich School of Engineering, University of Calgary, Calgary, Alberta, Canada.
J Invest Dermatol. 2018 Oct;138(10):2111-2122. doi: 10.1016/j.jid.2018.04.010. Epub 2018 Apr 26.
Hair follicle stem cells are regulated by intrafollicular and extrafollicular niche signals. Appropriate hair follicle regeneration relies on the coordinated release and integration of these signals. How immune cells, particularly cutaneous macrophages, influence the hair follicle stem cell niche and regeneration is not well understood. We took advantage of wound-induced hair growth (WIHG) to explore the relationship between wound macrophages and hair follicle regeneration. First, we showed that WIHG is dependent on CD11bF4/80 macrophages at 7-11 days after injury. Next, using CXCR1:CCR2 mice to capture the dynamic spectrum of macrophage phenotypes during wound healing, we showed that wound macrophages transition from a CXCR1 to a CXCR1 phenotype at the onset of WIHG. Finally, WIHG is abolished in mice deficient for CXCR1, delayed with pharmacological inhibition of transforming growth factor-β receptor type 1, and rescued with exogenous transforming growth factor-β1. Overall, we propose a model in which transforming growth factor-β1 and CXCR1 are critical for recruiting and maintaining the CCR2CXCR1Ly6CTNFα macrophages critical for stimulating WIHG.
毛囊干细胞受毛囊内和毛囊外龛信号的调控。适当的毛囊再生依赖于这些信号的协调释放和整合。免疫细胞，特别是皮肤巨噬细胞，如何影响毛囊干细胞龛和再生还不太清楚。我们利用创伤诱导的毛发生长（WIHG）来探索创伤巨噬细胞与毛囊再生之间的关系。首先，我们表明，在损伤后 7-11 天，WIHG 依赖于 CD11bF4/80 巨噬细胞。接下来，使用 CXCR1:CCR2 小鼠来捕获创伤愈合过程中巨噬细胞表型的动态谱，我们表明，创伤巨噬细胞在 WIHG 开始时从 CXCR1 向 CXCR1 表型转变。最后，CXCR1 缺陷小鼠的 WIHG 被消除，转化生长因子-β 受体 1 的药理学抑制延迟，外源性转化生长因子-β1 挽救。总的来说，我们提出了一个模型，其中转化生长因子-β1 和 CXCR1 对于招募和维持 CCR2CXCR1Ly6CTNFα 巨噬细胞对于刺激 WIHG 是至关重要的。
