The resolution of inflammation facilitates proper wound healing and limits tissue repair short of exaggerated fibrotic scarring. The atypical chemokine receptor (ACKR)2/D6 scavenges inflammatory chemokines, while IFN-β is a recently unveiled pro-resolving cytokine. Both effector molecules limit acute inflammatory episodes and promote their resolution in various organs. Here, we found fibrotic skin lesions from ACKR2^−/− mice presented increased epidermal and dermal thickening, atrophy of the subcutaneous adipose tissue, augmented disorientation of collagen deposition, and enhanced deformation and loss of hair follicles compared to WT counterparts. In addition, affected skin sections from ACKR2^−/− mice contained reduced levels of the pro-resolving mediators IFN-β and IL-10, but increased levels of the pro-inflammatory chemokines CCL2 and 3, the pro-fibrotic cytokine TGF-β, and the immune-stimulating cytokine IL-12. Notably, treatment with exogenous IFN-β rescued, at least in part, all the pro-fibrotic outcomes and lesion size in ACKR2^−/− mice and promoted expression of the pro-resolving enzyme 12/15-lipoxygenase (LO) in both ACKR2^−/− and WT mice. Moreover, Ifnb^−/− mice displayed enhanced pro-fibrotic indices upon exposure to bleomycin. These findings suggest ACKR2 is an important mediator in limiting inflammatory skin fibrosis and acts via IFN-β production to promote the resolution of inflammation and minimize tissue scaring.

中文翻译：

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ACKR2 通过 IFN-β 限制皮肤纤维化和脱发

炎症的消退促进了适当的伤​​口愈合并限制了组织修复，避免了过度的纤维化瘢痕形成。非典型趋化因子受体 (ACKR)2/D6 清除炎症趋化因子，而 IFN-β 是最近公布的促消退细胞因子。两种效应分子都限制急性炎症发作并促进其在各种器官中的消退。在这里，我们发现来自 ACKR2 ^-/-小鼠的纤维化皮肤病变与 WT 对应物相比，表皮和真皮增厚增加，皮下脂肪组织萎缩，胶原沉积定向障碍增加，以及毛囊变形和损失增加。此外，来自 ACKR2 的受影响皮肤部分^-/-小鼠的促分解介质 IFN-β 和 IL-10 水平降低，但促炎趋化因子 CCL2 和 3、促纤维化细胞因子 TGF-β 和免疫刺激细胞因子 IL-12 水平升高。值得注意的是，外源性 IFN-β 治疗至少部分挽救了 ACKR2 ^-/-小鼠中的所有促纤维化结果和病变大小，并促进了两种 ACKR2 中促分解酶 12/15-脂肪氧合酶 (LO) 的表达^-/-和 WT 小鼠。此外，Ifnb ^-/-小鼠在接触博莱霉素后显示出增强的促纤维化指数。这些发现表明 ACKR2 是限制炎症性皮肤纤维化的重要介质，并通过产生 IFN-β 来促进炎症消退并最大程度地减少组织疤痕。