MYC-mediated early glycolysis negatively regulates proinflammatory responses by controlling IRF4 in inflammatory macrophages

被引：47

作者：

Bae, Seyeon ^{[1
,2
]}

Park, Peter Sang Uk ^{[1
]}

Lee, Yeji ^{[1
]}

Mun, Se Hwan ^{[1
]}

Giannopoulou, Eugenia ^{[1
,3
]}

Fujii, Takayuki ^{[1
,4
]}

Lee, Kelvin P. ^{[5
]}

Violante, Sara Nunes ^{[6
]}

Cross, Justin R. ^{[6
]}

Park-Min, Kyung-Hyun ^{[1
,2
,7
]}

机构：

[1] Hosp Special Surg, Arthrit & Tissue Degenerat Program, David Z Rosensweig Genom Res Ctr, 535 E 70th St, New York, NY 10021 USA

[2] Weill Cornell Med Coll, Dept Med, New York, NY 10065 USA

[3] CUNY, New York City Coll Technol, Biol Sci Dept, Brooklyn, NY 11210 USA

[4] Kyoto Univ, Grad Sch Med, Dept Adv Med Rheumat Dis, Kyoto, Japan

[5] Roswell Park Comprehens Canc Ctr, Dept Immunol, Buffalo, NY USA

[6] Mem Sloan Kettering Canc Ctr, Donald B & Catherine C Marron Canc Metab Ctr, 1275 York Ave, New York, NY 10021 USA

[7] Weill Cornell Grad Sch Med Sci, BCMB Allied Program, New York, NY 10065 USA

来源：

CELL REPORTS | 2021年 / 35卷 / 11期

基金：

美国国家卫生研究院;

关键词：

COLONY-STIMULATING FACTOR; C-MYC; DIFFERENTIAL EXPRESSION; SUCCINATE-DEHYDROGENASE; CELLULAR-METABOLISM; SIGNAL; IMMUNITY; ACTIVATION; PROTEIN; GLUTAMINOLYSIS;

D O I：

10.1016/j.celrep.2021.109264

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

MYC activates different metabolic programs in a cell-type- and cell-status-dependent manner. However, the role of MYC in inflammatory macrophages has not yet been determined. Metabolic and molecular analyses reveal that MYC, but not hypoxia inducible factor 1 (HIF1), is involved in enhancing early glycolytic flux during inflammatory macrophage polarization. Ablation of MYC decreases lactate production by regulating lactate dehydrogenase (LDH) activity and causes increased inflammatory cytokines by regulating interferon regulatory factor 4 (IRF4) in response to lipopolysaccharide. Moreover, myeloid-specific deletion of MYC and pharmacological inhibition of the MYC/LDH axis enhance inflammation and the bacterial clearance in vivo. These results elucidate the potential role of the MYC/LDH/IRF4 axis in inflammatory macrophages by connecting early glycolysis with inflammatory responses and suggest that modulating early glycolytic flux mediated by the MYC/LDH axis can be used to open avenues for the therapeutic modulation of macrophage polarization to fight against bacterial infection.

引用

页数：22

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