title: Distinct regulation of tonsillar immune response in virus infection.
abstract: BACKGROUND
  The relationships between tonsillar immune responses, and viral infection and allergy are incompletely known.
  
  
  OBJECTIVE
  To study intratonsillar/nasopharyngeal virus detections and in vivo expressions of T-cell- and innate immune response-specific cytokines, transcription factors, and type I/II/III interferons in human tonsils.
  
  
  METHODS
  Palatine tonsil samples were obtained from 143 elective tonsillectomy patients. Adenovirus, bocavirus-1, coronavirus, enteroviruses, influenza virus, metapneumovirus, parainfluenza virus, rhinovirus, and respiratory syncytial virus were detected using PCR. The mRNA expression levels of IFN-α, IFN-β, IFN-γ, IL-10, IL-13, IL-17, IL-28, IL-29, IL-37, TGF-β, FOXP3, GATA3, RORC2, and Tbet were directly analyzed by quantitative RT-PCR.
  
  
  RESULTS
  Fifty percentage of subjects reported allergy, 59% had ≥1 nasopharyngeal viruses, and 24% had ≥1 intratonsillar viruses. Tonsillar virus detection showed a strong negative association with age; especially rhinovirus or parainfluenza virus detection showed positive association with IFN-γ and Tbet expressions. IL-37 expression was positively associated with atopic dermatitis, whereas IFN-α, IL-13, IL-28, and Tbet expressions were negatively associated with allergic diseases. Network analyses demonstrated strongly polarized clusters of immune regulatory (IL-10, IL-17, TGF-β, FOXP3, GATA3, RORC2, Tbet) and antiviral (IFN-α, IFN-β, IL-28, IL-29) genes. These two clusters became more distinctive in the presence of viral infection or allergy. A negative correlation between antiviral cytokines and IL-10, IL-17, IL-37, FOXP3, and RORC2 was observed only in the presence of viruses, and interestingly, IL-13 strongly correlated with antiviral cytokines.
  
  
  CONCLUSIONS
  Tonsillar cytokine expression is closely related to existing viral infections, age, and allergic illnesses and shows distinct clusters between antiviral and immune regulatory genes.
authors.affiliation: Department of Pediatrics, Turku University Hospital, Turku, Finland.
authors.forename: T
authors.initials: T
authors.lastname: Jartti
authors.forename: O
authors.initials: O
authors.lastname: Palomares
authors.forename: M
authors.initials: M
authors.lastname: Waris
authors.forename: O
authors.initials: O
authors.lastname: Tastan
authors.forename: R
authors.initials: R
authors.lastname: Nieminen
authors.forename: T
authors.initials: T
authors.lastname: Puhakka
authors.forename: B
authors.initials: B
authors.lastname: Rückert
authors.forename: A
authors.initials: A
authors.lastname: Aab
authors.forename: T
authors.initials: T
authors.lastname: Vuorinen
authors.forename: T
authors.initials: T
authors.lastname: Allander
authors.forename: T
authors.initials: T
authors.lastname: Vahlberg
authors.forename: O
authors.initials: O
authors.lastname: Ruuskanen
authors.forename: M
authors.initials: M
authors.lastname: Akdis
authors.forename: C A
authors.initials: CA
authors.lastname: Akdis
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D016000:Cluster Analysis; D016207:Cytokines / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D006801:Humans; D008297:Male; D014066:Palatine Tonsil / Q000276:immunology* / Q000378:metabolism / Q000821:virology*; D014157:Transcription Factors / Q000235:genetics; D059467:Transcriptome; D014777:Virus Diseases / Q000235:genetics / Q000276:immunology*; D055815:Young Adult
chemical_list: D016207:Cytokines; D014157:Transcription Factors
keywords: Allergy; T cell; cytokine; tonsil; virus