Progranulin Improves Acute Lung Injury through Regulating the Differentiation of Regulatory T Cells and Interleukin-10 Immunomodulation to Promote Macrophage Polarization
Progranulin Improves Acute Lung Injury through Regulating the Differentiation of Regulatory T Cells and Interleukin-10 Immunomodulation to Promote Macrophage Polarization
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颗粒体蛋白前体通过调节调节性 T 细胞的分化和白细胞介素 10 免疫调节促进巨噬细胞极化来改善急性肺损伤
DOI：
10.1155/2020/9704327
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发表时间：
2020-05-31
影响因子：
4.6
通讯作者：
Lin, Shi-hui
中科院分区：
文献类型：
--
作者：
Chen, Yan-qing;Wang, Chuan-jiang;Lin, Shi-hui
颗粒体蛋白前体（PGRN）在急性肺损伤（ALI）中发挥抗炎作用，有望成为一种潜在的药物。研究表明，调节性 T 细胞 (Treg) 和白介素 (IL-) 10 可以抑制 ALI 期间的炎症并减轻组织损伤。在本研究中，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作用。我们发现PGRN治疗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比例的增加与肺损伤严重程度的减轻、促炎细胞因子的减少和抗炎细胞因子的增加相一致。在体外，PGRN 治疗后，来自脾脏初始 CD4+ T 细胞的 CD4+CD25+FOXP3+ Tregs 的百分比增加。进一步研究发现PGRN可以调节抗炎因子IL-10，通过上调IL-10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 免疫调节在 ALI 中发挥保护作用。
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.