RT Journal Article
SR Electronic
T1 T-helper cell type-1 transcription factor T-bet is upregulated in pulmonary sarcoidosis
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP 1136
OP 1144
DO 10.1183/09031936.00089910
VO 38
IS 5
A1 E. Kriegova
A1 R. Fillerova
A1 T. Tomankova
A1 B. Hutyrova
A1 F. Mrazek
A1 T. Tichy
A1 V. Kolek
A1 R.M. du Bois
A1 M. Petrek
YR 2011
UL http://erj.ersjournals.com/content/38/5/1136.abstract
AB 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.