title: Programmed cell death ligand 2 regulates TH9 differentiation and induction of chronic airway hyperreactivity.
abstract: BACKGROUND
  Asthma is defined as a chronic inflammatory disease of the airways; however, the underlying physiologic and immunologic processes are not fully understood.
  
  
  OBJECTIVE
  The aim of this study was to determine whether TH9 cells develop in vivo in a model of chronic airway hyperreactivity (AHR) and what factors control this development.
  
  
  METHODS
  We have developed a novel chronic allergen exposure model using the clinically relevant antigen Aspergillus fumigatus to determine the time kinetics of TH9 development in vivo.
  
  
  RESULTS
  TH9 cells were detectable in the lungs after chronic allergen exposure. The number of TH9 cells directly correlated with the severity of AHR, and anti-IL-9 treatment decreased airway inflammation. Moreover, we have identified programmed cell death ligand (PD-L) 2 as a negative regulator of TH9 cell differentiation. Lack of PD-L2 was associated with significantly increased TGF-β and IL-1α levels in the lungs, enhanced pulmonary TH9 differentiation, and higher morbidity in the sensitized mice.
  
  
  CONCLUSIONS
  Our findings suggest that PD-L2 plays a pivotal role in the regulation of TH9 cell development in chronic AHR, providing novel strategies for modulating adaptive immunity during chronic allergic responses.
authors.affiliation: Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033-9605, USA.
authors.forename: Jerome
authors.initials: J
authors.lastname: Kerzerho
authors.forename: Hadi
authors.initials: H
authors.lastname: Maazi
authors.forename: Anneliese O
authors.initials: AO
authors.lastname: Speak
authors.forename: Natacha
authors.initials: N
authors.lastname: Szely
authors.forename: Vincent
authors.initials: V
authors.lastname: Lombardi
authors.forename: Bryant
authors.initials: B
authors.lastname: Khoo
authors.forename: Stacey
authors.initials: S
authors.lastname: Geryak
authors.forename: Jonathan
authors.initials: J
authors.lastname: Lam
authors.forename: Pejman
authors.initials: P
authors.lastname: Soroosh
authors.forename: Jacques
authors.initials: J
authors.lastname: Van Snick
authors.forename: Omid
authors.initials: O
authors.lastname: Akbari
mesh_terms: D056704:Adaptive Immunity; D000485:Allergens / Q000276:immunology; D000818:Animals; D000906:Antibodies / Q000276:immunology; D001232:Aspergillus fumigatus / Q000276:immunology; D016535:Bronchial Hyperreactivity / Q000235:genetics* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D002454:Cell Differentiation / Q000276:immunology; D002908:Chronic Disease; D004195:Disease Models, Animal; D005260:Female; D005786:Gene Expression Regulation; D053582:Interleukin-1alpha / Q000276:immunology; D016906:Interleukin-9 / Q000276:immunology*; D008168:Lung / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D018655:Lymphocyte Count; D051379:Mice; D008807:Mice, Inbred BALB C; D061027:Programmed Cell Death 1 Ligand 2 Protein / Q000235:genetics* / Q000276:immunology; D012720:Severity of Illness Index; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000473:pathology; D016212:Transforming Growth Factor beta / Q000276:immunology
chemical_list: D000485:Allergens; D000906:Antibodies; D053582:Interleukin-1alpha; D016906:Interleukin-9; C556978:Pdcd1lg2 protein, mouse; D061027:Programmed Cell Death 1 Ligand 2 Protein; D016212:Transforming Growth Factor beta