Subcutaneous administration of α-GalCer activates iNKT10 cells to promote M2 macrophage polarization and ameliorates chronic inflammation of obese adipose tissue

皮下注射 α-GalCer 可激活 iNKT10 细胞,促进 M2 巨噬细胞极化并改善肥胖脂肪组织的慢性炎症

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作者:Dongzhi Chen, Huijuan Zhao, Xiang Gao, Shengde Chen, Huifang Liu, Jingnan Zhang, Jinku Zhang, Ming Meng

Conclusion

The imbalance between the proportions of iNKT1 and iNKT10 cells may be involved in the development of chronic inflammation in obese adipose tissue. Administration of α-GalCer by subcutaneous injection in HFD-fed mice activates adipose tissue iNKT10 cells, which promote M2 macrophage polarization and improve chronic inflammation in obese adipose tissue.

Methods

C57BL/6J mice were fed high-fat diet (HFD) for 12 weeks to establish the obese mouse model. The pathology of adipose tissue was observed by H&E staining. The rates of iNKT cells, macrophages and cell subsets in adipose tissue were detected by FCM. Cytokine levels in serum and adipose tissue lymphocyte-stimulated supernatants were assessed with the CBA kit. The expression levels of related transcription factor in adipose tissue were detected by Western blot.

Objective

The role of iNKT cells was investigated in chronic adipose tissue inflammation in obese mice after administration of α-GalCer in different pathways.

Results

The proportions of iNKT cells, iNKT10 cells and M2 macrophages were decreased, while those of iNKT1 and M1 macrophages were increased in adipose tissue of HFD-fed mice. The expression levels of the related transcriptional proteins E4BP4 and Arg-1 were decreased while iNOS expression was increased in adipose tissue. Administration of α-GalCer by subcutaneous injection resulted in increased rates of iNKT10 cells and M2 macrophages, and decreased amounts of M1 macrophages in adipose tissue of HFD-fed mice. The expression of E4BP4 and Arg-1 were up-regulated, but iNOS was down-regulated. Meanwhile, infiltration of inflammatory cells into adipose tissue was further reduced.

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