title: Enhanced Th2 cell differentiation and function in the absence of Nox2.
abstract: BACKGROUND
  Patients with chronic granulomatous disease (CGD), whom inherit abnormal function of NADPH oxidase 2 (Nox2), suffer from hyperinflammatory responses in lung as well as bacterial and fungal infection. There have been studies to reveal the function of Nox2 in hyperinflammatory diseases, especially in asthma, but the exact role of Nox2 in asthma is still unclear and controversial. Therefore, we attempted to clarify the exact role of Nox2 in asthma, using various experimental asthma models.
  
  
  METHODS
  Asthma phenotypes were analyzed in response to various allergen-induced experimental asthma using Nox2-deficient mice and recombinase gene-activating-1-deficient mice. To understand the underlying mechanisms of exaggerated Th2 effector functions, we investigated the degree of T-cell activation, levels of activation-induced cell death (AICD), and regulatory T (Treg)-cell differentiation in Nox2-deficient T cells.
  
  
  RESULTS
  Asthma phenotypes were increased through enhanced Th2 differentiation and function in Nox2-null mice regardless of dose and route of various allergens. Nox2-deficient T cells also showed hyperactivation, reduced AICD, and diminished Treg-cell differentiation through increased AKT phosphorylation (T308/S473) and enhanced mitochondrial ROS production.
  
  
  CONCLUSIONS
  Our findings indicate that Nox2 deficiency results in exaggerated experimental asthma, which is caused by enhanced Th2 effector function in a T-cell-intrinsic manner.
authors.affiliation: Graduate School of Medical Science and Engineering (GSMSE), Biomedical Research Center, KAIST Institute of the BioCentury, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Korea.|K-herb Research Center, Korea Institute of Oriental Medicine, Daejeon, Korea.
authors.forename: B-I
authors.initials: BI
authors.lastname: Kwon
authors.affiliation: Graduate School of Medical Science and Engineering (GSMSE), Biomedical Research Center, KAIST Institute of the BioCentury, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Korea.
authors.forename: T W
authors.initials: TW
authors.lastname: Kim
authors.affiliation: Graduate School of Medical Science and Engineering (GSMSE), Biomedical Research Center, KAIST Institute of the BioCentury, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Korea.|Department of Dermatology, School of Medicine, Pusan National University, Busan, Korea.
authors.forename: K
authors.initials: K
authors.lastname: Shin
authors.affiliation: Graduate School of Medical Science and Engineering (GSMSE), Biomedical Research Center, KAIST Institute of the BioCentury, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Korea.|Korean Medicine Convergence Research Division, Korea Institute of Oriental Medicine, Daejeon, Korea.
authors.forename: Y H
authors.initials: YH
authors.lastname: Kim
authors.affiliation: Graduate School of Medical Science and Engineering (GSMSE), Biomedical Research Center, KAIST Institute of the BioCentury, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Korea.
authors.forename: C M
authors.initials: CM
authors.lastname: Yuk
authors.affiliation: Department of Microbiology, Infection Signaling Network Research Center, Chungnam National University School of Medicine, Daejeon, Korea.
authors.forename: J-M
authors.initials: JM
authors.lastname: Yuk
authors.affiliation: Department of Microbiology, Infection Signaling Network Research Center, Chungnam National University School of Medicine, Daejeon, Korea.
authors.forename: D-M
authors.initials: DM
authors.lastname: Shin
authors.affiliation: Department of Microbiology, Infection Signaling Network Research Center, Chungnam National University School of Medicine, Daejeon, Korea.
authors.forename: E-K
authors.initials: EK
authors.lastname: Jo
authors.affiliation: Animal Model Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Korea.
authors.forename: C-H
authors.initials: CH
authors.lastname: Lee
authors.affiliation: Graduate School of Medical Science and Engineering (GSMSE), Biomedical Research Center, KAIST Institute of the BioCentury, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Korea.
authors.forename: S-H
authors.initials: SH
authors.lastname: Lee
mesh_terms: D000485:Allergens / Q000276:immunology; D000818:Animals; D001249:Asthma / Q000175:diagnosis / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics* / Q000276:immunology*; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D018450:Disease Progression; D006105:Granulomatous Disease, Chronic / Q000175:diagnosis / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D008168:Lung / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D000074662:NADPH Oxidase 2 / Q000172:deficiency*; D010641:Phenotype; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000166:cytology* / Q000502:physiology*
chemical_list: D000485:Allergens; D016207:Cytokines; D000074662:NADPH Oxidase 2
keywords: 
  AKT
  ; Nox2; Th2 cell; allergic asthma; mitochondrial ROS