title: T-bet and interleukin-27: possible TH1 immunomodulators of sarcoidosis.
abstract: BACKGROUND
  Sarcoidosis has often been termed an "immune paradox" as there is peripheral anergy to common recall antigens despite pronounced TH1-dominant inflammation at disease sites, such as the lung, with up-regulation of interferon γ, IL-27 and transcription factors. Peripheral blood may reflect the anergic state, while exhaled breath condensate (EBC) analysis may offer insights into the lung disease.
  
  
  METHODS
  A cross-sectional study was conducted to investigate the expression of TH1 cytokines and transcription factors (IFNγ, IL-27 and T-bet) in the peripheral blood and/or EBC of sarcoidosis patients and healthy controls. Whole blood and EBC were collected from sarcoidosis patients and healthy controls. TH1 cytokine expression levels were then measured in peripheral blood mononuclear cells (PBMCs) and/or plasma and EBC using quantitative real-time PCR, ELISA and via Western blotting.
  
  
  RESULTS
  Compared to healthy controls, PBMC IL-27 mRNA was higher in patients (p = 0.0019). There were no significant differences in plasma IL-27 protein between patients and controls (p = 0.20). T-bet mRNA and protein were lower (p = 0.010 and p = 0.0043, respectively) in patients compared to controls. There were no significant differences in PBMC IFNγ mRNA and protein expression (p = 0.68 and p = 0.74, respectively) nor in EBC IL-27 levels.
  
  
  CONCLUSIONS
  Our data indicate that depressed T-bet mRNA and protein expression could contribute to the peripheral anergy in sarcoidosis and that IL-27 mRNA levels are elevated in the PBMC from those with sarcoidosis.
authors.affiliation: School of Medical Sciences, Inflammation and Infection Research Centre, UNSW, Sydney, 2052, Australia. joshua_loke_w_s@hotmail.com.|Department of Respiratory Medicine, Prince of Wales Hospital, Randwick, NSW, 2031, Australia. joshua_loke_w_s@hotmail.com.
authors.forename: Wei Sheng Joshua
authors.identifier: http://orcid.org/0000-0001-6496-1546
authors.initials: WS
authors.lastname: Loke
authors.affiliation: School of Medical Sciences, Inflammation and Infection Research Centre, UNSW, Sydney, 2052, Australia. araluen.freeman@unsw.edu.au.
authors.forename: Araluen
authors.initials: A
authors.lastname: Freeman
authors.affiliation: School of Medical Sciences, Inflammation and Infection Research Centre, UNSW, Sydney, 2052, Australia. l.garthwaite@unsw.edu.au.
authors.forename: Linda
authors.initials: L
authors.lastname: Garthwaite
authors.affiliation: School of Medical Sciences, Inflammation and Infection Research Centre, UNSW, Sydney, 2052, Australia. s.prazakova@unsw.edu.au.|Department of Respiratory Medicine, Prince of Wales Hospital, Randwick, NSW, 2031, Australia. s.prazakova@unsw.edu.au.
authors.forename: Silvie
authors.initials: S
authors.lastname: Prazakova
authors.affiliation: School of Medical Sciences, Inflammation and Infection Research Centre, UNSW, Sydney, 2052, Australia. mijeong.park@unsw.edu.au.
authors.forename: Mijeong
authors.initials: M
authors.lastname: Park
authors.affiliation: School of Medical Sciences, Inflammation and Infection Research Centre, UNSW, Sydney, 2052, Australia. k.hsu@unsw.edu.au.
authors.forename: Kenneth
authors.initials: K
authors.lastname: Hsu
authors.affiliation: School of Medical Sciences, Inflammation and Infection Research Centre, UNSW, Sydney, 2052, Australia. paul.thomas@unsw.edu.au.|Department of Respiratory Medicine, Prince of Wales Hospital, Randwick, NSW, 2031, Australia. paul.thomas@unsw.edu.au.
authors.forename: Paul S
authors.initials: PS
authors.lastname: Thomas
authors.affiliation: School of Medical Sciences, Inflammation and Infection Research Centre, UNSW, Sydney, 2052, Australia. c.herbert@unsw.edu.au.
authors.forename: Cristan
authors.initials: C
authors.lastname: Herbert
mesh_terms: D000328:Adult; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D007155:Immunologic Factors / Q000096:biosynthesis* / Q000276:immunology; D007378:Interleukins / Q000096:biosynthesis* / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D012507:Sarcoidosis / Q000276:immunology / Q000378:metabolism*; D020825:T-Box Domain Proteins / Q000096:biosynthesis* / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism*; D055815:Young Adult; D000098815:T-bet Transcription Factor
chemical_list: D007155:Immunologic Factors; D007378:Interleukins; C464565:MYDGF protein, human; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor
keywords: Anergy; IL-27; Interferon-γ; Sarcoidosis; T-bet; TH1