title: [FLT3 signaling manipulates conventional dendritic cells to regulate acute lung injury].
abstract: OBJECTIVE
  To explore the effects of FLT3 signaling on the accumulation and maturation of pulmonary conventional dendritic cells (cDCs) and determine whether or not the inhibition of FLT3 signaling may attenuate acute lung inflammation/injury (ALI).
  
  
  METHODS
  C57BL/6 mice were pretreated separately with FLT3-ligand (FLT3L) and lestaurtinib for 5 days. Murine model of ALI was subsequently induced by an intra-tracheal instillation of lipopolysaccharide (LPS) and lung specimens were harvested 24 hours later. The accumulation and maturation status of pulmonary cDCs were assessed by flow cytometry. Lung myeloperoxidase (MPO) activity was measured to evaluate the infiltration of neutrophils. The ratio between transcription factors T-bet and GATA-3 mRNA was determined to estimate the balance of Th1/Th2 response. Lung injury was estimated by lung wet weight/body weight ratio (LWW/BW) and histopathological assessment.
  
  
  RESULTS
  LPS challenge resulted in rapid accumulation and maturation of pulmonary cDCs. FLT3L pretreatment further stimulated the accumulation and maturation of pulmonary cDCs, leading to a marked deterioration of LWW/BW and lung histopathological changes. Meanwhile, the lung MPO activity and T-bet/GATA-3 mRNA ratio were boosted by the administration of FLT3L. In contrast, the lestaurtinib pretreatment inhibited the accumulation and maturation of pulmonary cDCs, leading to a significant improvement of LWW/BW and lung histopathological changes. The administration of lestaurtinib also suppressed the lung MPO activity and T-bet/GATA-3 mRNA ratio in the lung.
  
  
  CONCLUSIONS
  FLT3 signaling attenuates ALI by regulating the accumulation and maturation of pulmonary cDCs, indicating a potential pharmacotherapy for ALI.
authors: Department of Critical Care Medicine, Nanjing Zhongda Hospital, Southeast University, Nanjing 210009, China.
authors: Liang
authors: L
authors: Dong
authors: Jing-yuan
authors: JY
authors: Xu
authors: Jun
authors: J
authors: Liu
authors: Xiao-min
authors: XM
authors: Lu
authors: Yi
authors: Y
authors: Yang
authors: Hai-bo
authors: HB
authors: Qiu
mesh_terms: D055371:Acute Lung Injury / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D003713:Dendritic Cells / Q000166:cytology / Q000378:metabolism*; D050990:GATA3 Transcription Factor / Q000378:metabolism; D007249:Inflammation; D008297:Male; D008565:Membrane Proteins / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D015398:Signal Transduction; D020825:T-Box Domain Proteins / Q000378:metabolism; D051941:fms-Like Tyrosine Kinase 3 / Q000378:metabolism*; D000098815:T-bet Transcription Factor
chemical_list: D050990:GATA3 Transcription Factor; C494748:Gata3 protein, mouse; D008565:Membrane Proteins; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; C084881:flt3 ligand protein; C497971:Flt3 protein, mouse; D051941:fms-Like Tyrosine Kinase 3