title: STAT4 knockout protects LPS-induced lung injury by increasing of MDSC and promoting of macrophage differentiation.
abstract: The disruption of signal transducer and activator of transcription 4 (STAT4) signal can inhibit the inflammation and protect organs from injury during severe bacterial infection. However, the mechanism of STAT4 signal in lung injury remains poor understood. Here we report that STAT4 deficiency decreased the lethality and protein leakage in STAT4(-/-) mice and protected lipopolysaccharid (LPS)-induced lung injury with ameliorated edema, inflammatory infiltration and hemorrhage. The expression of CD11b(+)Gr-1(+) myeloid derived suppressor cells (MDSCs) markedly increased in the circulation of STAT4(-/-) mice after LPS stimuli, accompanying with increased macrophages infiltration in inflamed lung tissue. In addition, the levels of pro-inflammatory cytokines including tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6 decreased while anti-inflammatory cytokine (IL-10) increased in the bronchoalveolar lavage fluid of STAT4(-/-) mice. Thus, these results indicate that the accumulation of MDSCs and macrophages play a critical role in LPS-induced lung injury. Targeting MDSCs and macrophages polarization through a STAT4 dependent signaling pathway might help to reduce the inflammation and damage of lung tissue.
authors.affiliation: Department of Respiratory Medicine, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
authors.forename: Cuiping
authors.initials: C
authors.lastname: Fu
authors.affiliation: Department of Respiratory Medicine, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai 200030, China.
authors.forename: Liyan
authors.initials: L
authors.lastname: Jiang
authors.affiliation: Department of Respiratory Medicine, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
authors.forename: Xiaobo
authors.initials: X
authors.lastname: Xu
authors.affiliation: Department of Respiratory Medicine, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
authors.forename: Fen
authors.initials: F
authors.lastname: Zhu
authors.affiliation: Department of Respiratory Medicine, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
authors.forename: Shuqi
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of Respiratory Medicine, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Wu
authors.affiliation: Department of Respiratory Medicine, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
authors.forename: Zilong
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai 200032, China. Electronic address: yang.xiangdong@zs-hospital.sh.cn.
authors.forename: Xiangdong
authors.initials: X
authors.lastname: Yang
authors.affiliation: Department of Respiratory Medicine, Zhongshan Hospital, Fudan University, Shanghai 200032, China. Electronic address: li.shanqun@zs-hospital.sh.cn.
authors.forename: Shanqun
authors.initials: S
authors.lastname: Li
mesh_terms: D000818:Animals; D039481:CD11b Antigen; D016207:Cytokines / Q000378:metabolism*; D004195:Disease Models, Animal; D008070:Lipopolysaccharides / Q000494:pharmacology; D055370:Lung Injury / Q000139:chemically induced / Q000276:immunology* / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D022423:Myeloid Cells / Q000378:metabolism*; D050797:STAT4 Transcription Factor / Q000378:metabolism*
chemical_list: D039481:CD11b Antigen; D016207:Cytokines; D008070:Lipopolysaccharides; D050797:STAT4 Transcription Factor; C494091:Stat4 protein, mouse
keywords: Lung injury; MDSCs; Macrophages; STAT4