TGF-β promotes glycolysis through PFKL in activated macrophages and exacerbates sepsis by disrupting blood coagulation

Abstract The metabolism of macrophages plays a key role in their immune responses, but the mechanisms by which is regulated remain largely unknown. We show here that TGF-β induces unique phenotype and regulates glycolysis independently inflammatory cytokine production. Specifically, increased expression activity phosphofructokinase-1 liver type (PFKL) thus promoted during cell activation, yet paradoxically suppressed production proinflammatory cytokines same macrophages. upregulation was mediated an mTOR-c-MYC dependent pathway, whereas inhibition ascribed to downregulated activation major pro-inflammatory transcription factors, namely AP-1, NFkB STAT1. Importantly, we found LPS-induced sepsis model, enhancement macrophage led decreased survival mice increasing blood coagulation. Analysis cohorts patients with covid-19 revealed PFKL, TGF-b receptors TGFBRI coagulation factor F13A1 monocytes positively correlated progression disease. Thus, emerging as critical regulating could serve therapeutic target Covid-19.