Progranulin (PGRN), which plays an anti-inflammatory role in acute lung injury (ALI), is promising as a potential drug. Studies have shown that regulatory T cells (Tregs) and interleukin- (IL-) 10 can repress inflammation and alleviate tissue damage during ALI. In this study, we built a lipopolysaccharide- (LPS-) induced ALI mouse model to illustrate the effect of PGRN on regulation of Treg differentiation and modulation of IL-10 promoting macrophage polarization. We found that the proportion of Tregs in splenic mononuclear cells and peripheral blood mononuclear cells was higher after treatment with PGRN. The increased proportion of Tregs after PGRN intratracheal instillation was consistent with the decreased severity of lung injury, the reduction of proinflammatory cytokines, and the increase of anti-inflammatory cytokines. In vitro, the percentages of CD4⁺CD25⁺FOXP3⁺ Tregs from splenic naïve CD4⁺ T cells increased after PGRN treatment. In further research, it was found that PGRN can regulate the anti-inflammatory factor IL-10 and affect the polarization of M1/M2 macrophages by upregulating IL-10. These findings show that PGRN likely plays a protective role in ALI by promoting Treg differentiation and activating IL-10 immunomodulation.

中文翻译：

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前颗粒蛋白可通过调节调节性T细胞的分化和IL-10免疫调节来促进巨噬细胞极化，从而改善急性肺损伤。

前颗粒蛋白（PGRN）在急性肺损伤（ALI）中起抗炎作用，有望成为一种潜在的药物。研究表明，调节性T细胞（Tregs）和白介素-（IL-）10可以抑制ALI期间的炎症并减轻组织损伤。在这项研究中，我们建立了脂多糖（LPS-）诱导的ALI小鼠模型，以说明PGRN对调节Treg分化和调节IL-10促进巨噬细胞极化的影响。我们发现，PGRN处理后，脾脏单个核细胞和外周血单个核细胞中Tregs的比例更高。PGRN气管内滴注后Tregs比例增加与肺损伤严重程度降低，促炎细胞因子减少和抗炎细胞因子增加相一致。在体外，PGRN处理后，脾脏初始CD4 ⁺ T细胞中CD4 ⁺ CD25 ⁺ FOXP3 ⁺ Tregs的百分比增加。在进一步的研究中，发现PGRN可以通过上调IL-10来调节抗炎因子IL-10并影响M1 / M2巨噬细胞的极化。这些发现表明，PGRN可能通过促进Treg分化和激活IL-10免疫调节而在ALI中起保护作用。