Department of Medicine, The Royal Melbourne Hospital, The University of Melbourne, Parkville, Victoria 3050, Australia;
Department of Pharmacology, The University of Melbourne, Parkville, Victoria 3050, Australia.
J Immunol. 2020 Jul 1;205(1):213-222. doi: 10.4049/jimmunol.2000315. Epub 2020 May 27.
It has been reported that a GM-CSF→CCL17 pathway, originally identified in vitro in macrophage lineage populations, is implicated in the control of inflammatory pain, as well as arthritic pain and disease. We explore, in this study and in various inflammation models, the cellular CCL17 expression and its GM-CSF dependence as well as the function of CCL17 in inflammation and pain. This study used models allowing the convenient cell isolation from reporter mice; it also exploited both CCL17-dependent and unique CCL17-driven inflammatory pain and arthritis models, the latter permitting a radiation chimera approach to help identify the CCL17 responding cell type(s) and the mediators downstream of CCL17 in the control of inflammation and pain. We present evidence that 1) in the particular inflammation models studied, CCL17 expression is predominantly in macrophage lineage populations and is GM-CSF dependent, 2) for its action in arthritic pain and disease development, CCL17 acts on CCR4 non-bone marrow-derived cells, and 3) for inflammatory pain development in which a GM-CSF→CCL17 pathway appears critical, nerve growth factor, CGRP, and substance P all appear to be required.
据报道，最初在巨噬细胞谱系群体中体外鉴定的 GM-CSF→CCL17 途径与炎症性疼痛以及关节炎疼痛和疾病的控制有关。在这项研究和各种炎症模型中，我们探讨了细胞 CCL17 表达及其对 GM-CSF 的依赖性，以及 CCL17 在炎症和疼痛中的作用。本研究使用了允许从报告小鼠中方便地分离细胞的模型；它还利用了 CCL17 依赖性和独特的 CCL17 驱动的炎症性疼痛和关节炎模型，后者允许采用放射嵌合体方法来帮助确定 CCL17 反应细胞类型和 CCL17 在炎症和疼痛控制中的下游介质。我们提出证据表明：1）在研究的特定炎症模型中，CCL17 表达主要在巨噬细胞谱系群体中，并且依赖于 GM-CSF；2）对于其在关节炎疼痛和疾病发展中的作用，CCL17 作用于 CCR4 非骨髓来源细胞；3）对于炎症性疼痛的发展，其中 GM-CSF→CCL17 途径似乎至关重要，神经生长因子、CGRP 和 P 物质似乎都需要。
