生物
细胞生物学
单核细胞
mTORC1型
树突状细胞
粒细胞巨噬细胞集落刺激因子
细胞因子
细胞分化
过氧化物酶体增殖物激活受体
癌症研究
受体
免疫学
免疫系统
信号转导
PI3K/AKT/mTOR通路
基因
生物化学
作者
Fernando Erra Díaz,Ignacio Mazzitelli,Lucía Bleichmar,Claudia Melucci,Asa Thibodeau,Tomás Dalotto Moreno,Radu Marcheş,Gabriel A. Rabinovich,Duygu Ucar,Jorge Geffner
出处
期刊:Cell Reports
[Elsevier]
日期:2023-03-01
卷期号:42 (3): 112156-112156
被引量:5
标识
DOI:10.1016/j.celrep.2023.112156
摘要
Monocytes can differentiate into macrophages (Mo-Macs) or dendritic cells (Mo-DCs). The cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF) induces the differentiation of monocytes into Mo-Macs, while the combination of GM-CSF/interleukin (IL)-4 is widely used to generate Mo-DCs for clinical applications and to study human DC biology. Here, we report that pharmacological inhibition of the nuclear receptor peroxisome proliferator-activated receptor gamma (PPARγ) in the presence of GM-CSF and the absence of IL-4 induces monocyte differentiation into Mo-DCs. Remarkably, we find that simultaneous inhibition of PPARγ and the nutrient sensor mammalian target of rapamycin complex 1 (mTORC1) induces the differentiation of Mo-DCs with stronger phenotypic stability, superior immunogenicity, and a transcriptional profile characterized by a strong type I interferon (IFN) signature, a lower expression of a large set of tolerogenic genes, and the differential expression of several transcription factors compared with GM-CSF/IL-4 Mo-DCs. Our findings uncover a pathway that tailors Mo-DC differentiation with potential implications in the fields of DC vaccination and cancer immunotherapy.
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