Autophagic reprogramming of bone marrow-derived macrophages

被引:6
|
作者
Mazher, Mayada [1 ,2 ]
Moqidem, Yomna Adel [1 ]
Zidan, Mona [2 ]
Sayed, Ahmed A. [2 ]
Abdellatif, Ahmed [1 ,3 ]
机构
[1] Amer Univ Cairo, Sch Sci & Engn, Biotechnol Program, Cairo 11835, Egypt
[2] Childrens Canc Hosp, Cairo 57357, Egypt
[3] Amer Univ Cairo, Sch Sci & Engn, Dept Biol, Cairo 11835, Egypt
关键词
Macrophages; Autophagy; Macrophage polarization; Autophagy-related genes; M1; macrophages; M2; KAPPA-B; ULK1; COMPLEX; EXPRESSION; PHAGOCYTOSIS; MECHANISM; PROTEINS; ATG16L1; ANGIOGENESIS; POLARIZATION; SECRETION;
D O I
10.1007/s12026-022-09344-2
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Macro-autophagy is a highly conserved catabolic process among eukaryotes affecting macrophages. This work studies the genetic regulatory network involving the interplay between autophagy and macrophage polarization (activation). Autophagy-related genes (Atgs) and differentially expressed genes (DEGs) of macrophage polarization (M1-M2) were predicted, and their regulatory networks constructed. Naive (M0) mouse bone marrow-derived monocytes were differentiated into M1 and M2a. Validation of the targets of Smad1, LC3A and LC3B, Atg16L1, Atg7, IL-6, CD68, Arg-1, and Vamp7 was performed in vitro. Immunophenotyping by flow cytometry revealed three macrophage phenotypes: M0 (IL-6 + /CD68 +), M1 (IL-6 + /CD68 + /Arg-1 +), and M2a (CD68 + /Arg-1). Confocal microscopy revealed increased autophagy in both M1 and M2a and a significant increase in the pre-autophagosomes size and number. Bafilomycin A increased the expression of CD68 and Arg-1 in all cell lineages. In conclusion, our approach predicted the protein targets mediating the interplay between autophagy and macrophage polarization. We suggest that autophagy reprograms macrophage polarization via CD68, arginase 1, Atg16L1-1, and Atg16L1-3. The current findings provide a foundation for the future use of macrophages in immunotherapy of different autoimmune disorders.
引用
收藏
页码:229 / 246
页数:18
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