title: T-helper cell type-1 transcription factor T-bet is upregulated in pulmonary sarcoidosis.
abstract: Upregulation of genes for interferon (IFN)-γ and CXC chemokine receptor (CXCR)3 expression, two crucial molecules in sarcoid inflammation and granuloma formation, is directly controlled by the T-helper (Th)1 transcription factor T-bet (T-box, expressed in T-cells). However, there is no information on T-bet expression in sarcoidosis or its relationship with "sarcoidosis-associated" genes. Therefore, we investigated expression of T-bet mRNA and, in parallel, a spectrum of genes known to be involved in sarcoidosis pathogenesis. Transcripts were determined in bronchoalveolar lavage (BAL) cells from 62 sarcoidosis patients and 25 controls by quantitative RT-PCR; T-bet protein was localised by immunohistochemistry. Patient's BAL cells expressed higher mRNA T-bet levels than those of controls (mean ± sd fold change 3.64 ± 1.72; p = 0.00006). T-bet mRNA expression did not vary between clinical phenotypes as assessed by chest radiography stage, presence/absence of Löfgren's syndrome, extrapulmonary/pulmonary involvement or progressing/remitting disease (p > 0.05). T-bet mRNA expression correlated with expression of IFN-γ, CC chemokine ligand 5, CXC chemokine ligand (CXC)10, interleukin (IL)-2 receptor/IL-15 receptor β, CXCR3 and CXCR6 (p < 0.01). T-bet protein was localised to alveolar macrophages and lymphocytes, tissue multinucleated giant cells, macrophages and lymphocytes. In pulmonary sarcoidosis, T-bet upregulation is associated with changes in expression of IFN-γ, CXCR3 and chemokines/receptors involved in the pathogenesis of sarcoidosis, which suggests a role for T-bet in this Th1 disease, including modulation of some sarcoidosis-associated genes.
authors.affiliation: Laboratory of Immunogenomics and Proteomics, Faculty of Medicine and Dentistry, Palacky University, Olomouc, Czech Republic.
authors.forename: E
authors.initials: E
authors.lastname: Kriegova
authors.forename: R
authors.initials: R
authors.lastname: Fillerova
authors.forename: T
authors.initials: T
authors.lastname: Tomankova
authors.forename: B
authors.initials: B
authors.lastname: Hutyrova
authors.forename: F
authors.initials: F
authors.lastname: Mrazek
authors.forename: T
authors.initials: T
authors.lastname: Tichy
authors.forename: V
authors.initials: V
authors.lastname: Kolek
authors.forename: R M
authors.initials: RM
authors.lastname: du Bois
authors.forename: M
authors.initials: M
authors.lastname: Petrek
mesh_terms: D000328:Adult; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D018946:Chemokine CCL5 / Q000235:genetics / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D008198:Lymph Nodes / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000378:metabolism; D054367:Receptors, CXCR3 / Q000235:genetics / Q000378:metabolism; D000075744:Receptors, CXCR6; D019707:Receptors, Chemokine / Q000235:genetics / Q000378:metabolism; D015375:Receptors, Interleukin-2 / Q000235:genetics / Q000378:metabolism; D011991:Receptors, Virus / Q000235:genetics / Q000378:metabolism; D017565:Sarcoidosis, Pulmonary / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D020825:T-Box Domain Proteins / Q000378:metabolism*; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism*; D015854:Up-Regulation; D000098815:T-bet Transcription Factor
chemical_list: C483024:CCL5 protein, human; C106330:CXCR6 protein, human; D018946:Chemokine CCL5; D012333:RNA, Messenger; D054367:Receptors, CXCR3; D000075744:Receptors, CXCR6; D019707:Receptors, Chemokine; D015375:Receptors, Interleukin-2; D011991:Receptors, Virus; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; D007371:Interferon-gamma