Cytokines produced by immune cells have been demonstrated to act on muscle stem cells (MuSCs) and direct their fate and behavior during muscle repair and regeneration. Nevertheless, it is unclear whether and how MuSCs can also in turn modulate the properties of immune cells. Here, we showed that in vitro expanded MuSCs exhibited a potent anti‐inflammatory effect when infused into mice suffering from inflammatory bowel disease (IBD). Supernatant conditioned by MuSCs similarly ameliorated IBD. This beneficial effect of MuSCs was not observed when macrophages were depleted. The MuSC supernatant was found to greatly attenuate the expression of inflammatory cytokines but increase the expression of programmed death‐ligand 1 in macrophages treated with lipopolysaccharide and interferon gamma. Further analysis revealed that MuSCs produce a large amount of insulin‐like growth factor‐2 (IGF‐2) that instructs maturing macrophages to undergo oxidative phosphorylation and thus acquire anti‐inflammatory properties. Interestingly, the IGF‐2 production by MuSCs is much higher than by mesenchymal stem cells. Knockdown or neutralization of IGF‐2 abrogated the anti‐inflammatory effects of MuSCs and their therapeutic efficacy on IBD. Our study demonstrated that MuSCs possess a strong anti‐inflammatory property and the bidirectional interactions between immune cells and MuSCs have important implications in muscle‐related physiological and pathological conditions.

中文翻译：

---

骨骼肌干细胞通过胰岛素样生长因子2赋予成熟的巨噬细胞抗炎特性。

已证明免疫细胞产生的细胞因子可作用于肌肉干细胞（MuSC），并在肌肉修复和再生过程中指导其命运和行为。然而，尚不清楚MuSCs是否以及如何还能进而调节免疫细胞的特性。在这里，我们表明，将体外扩增的MuSCs注入患有炎症性肠病（IBD）的小鼠时，表现出有效的抗炎作用。由MuSCs调节的上清液同样改善了IBD。当巨噬细胞耗尽时，未观察到MuSC的这种有益效果。在用脂多糖和干扰素γ处理的巨噬细胞中，发现MuSC上清液大大减弱了炎症细胞因子的表达，但增加了程序性死亡配体1的表达。进一步的分析表明，MuSCs产生大量的胰岛素样生长因子2（IGF-2），指示成熟的巨噬细胞进行氧化磷酸化，从而获得抗炎特性。有趣的是，MuSCs产生的IGF-2远高于间充质干细胞。剔除或中和IGF-2可消除MuSC的抗炎作用及其对IBD的治疗功效。我们的研究表明，MuSCs具有很强的抗炎特性，免疫细胞和MuSCs之间的双向相互作用对与肌肉相关的生理和病理状况具有重要意义。MuSCs产生的IGF-2远高于间充质干细胞。剔除或中和IGF-2可消除MuSC的抗炎作用及其对IBD的治疗功效。我们的研究表明，MuSCs具有很强的抗炎特性，免疫细胞和MuSCs之间的双向相互作用对与肌肉相关的生理和病理状况具有重要意义。MuSCs产生的IGF-2远高于间充质干细胞。剔除或中和IGF-2可消除MuSC的抗炎作用及其对IBD的治疗功效。我们的研究表明，MuSCs具有很强的抗炎特性，免疫细胞和MuSCs之间的双向相互作用对与肌肉相关的生理和病理状况具有重要意义。