Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, 315 Ferst Drive, Atlanta, GA, 30332, USA.
Department of Biomedical Engineering, University of Virginia, Box 800759, Charlottesville, VA, 22908, USA.
Sci Rep. 2017 Mar 27;7(1):447. doi: 10.1038/s41598-017-00477-1.
Successful tissue repair requires the activities of myeloid cells such as monocytes and macrophages that guide the progression of inflammation and healing outcome. Immunoregenerative materials leverage the function of endogenous immune cells to orchestrate complex mechanisms of repair; however, a deeper understanding of innate immune cell function in inflamed tissues and their subsequent interactions with implanted materials is necessary to guide the design of these materials. Blood monocytes exist in two primary subpopulations, characterized as classical inflammatory or non-classical. While classical monocytes extravasate into inflamed tissue and give rise to macrophages or dendritic cells, the recruitment kinetics and functional role of non-classical monocytes remains unclear. Here, we demonstrate that circulating non-classical monocytes are directly recruited to polymer films within skin injuries, where they home to a perivascular niche and generate alternatively activated, wound healing macrophages. Selective labeling of blood monocyte subsets indicates that non-classical monocytes are biased progenitors of alternatively activated macrophages. On-site delivery of the immunomodulatory small molecule FTY720 recruits S1PR3-expressing non-classical monocytes that support vascular remodeling after injury. These results elucidate a previously unknown role for blood-derived non-classical monocytes as contributors to alternatively activated macrophages, highlighting them as key regulators of inflammatory response and regenerative outcome.
成功的组织修复需要髓系细胞（如单核细胞和巨噬细胞）的活动，这些细胞可以指导炎症的进展和愈合结果。免疫再生材料利用内源性免疫细胞的功能来协调修复的复杂机制；然而，为了指导这些材料的设计，有必要更深入地了解炎症组织中固有免疫细胞的功能及其与植入材料的后续相互作用。血液单核细胞存在两种主要的亚群，分别为经典炎性或非经典型。虽然经典单核细胞渗出到炎症组织中，并分化为巨噬细胞或树突状细胞，但非经典单核细胞的募集动力学和功能作用仍不清楚。在这里，我们证明循环中的非经典单核细胞可被直接招募到皮肤损伤中的聚合物膜上，在那里它们归巢到血管周围龛位，并产生替代性激活的、促进伤口愈合的巨噬细胞。血液单核细胞亚群的选择性标记表明，非经典单核细胞是替代性激活的巨噬细胞的偏向祖细胞。免疫调节小分子 FTY720 的局部给药可招募表达 S1PR3 的非经典单核细胞，这些细胞在损伤后支持血管重塑。这些结果阐明了血液来源的非经典单核细胞作为替代性激活的巨噬细胞的贡献者的先前未知作用，强调了它们作为炎症反应和再生结果的关键调节因子的重要性。
