T-helper cell type-1 transcription factor T-bet is upregulated in pulmonary sarcoidosis
Language English Country Great Britain, England Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
21540308
DOI
10.1183/09031936.00089910
PII: 09031936.00089910
Knihovny.cz E-resources
- MeSH
- Bronchoalveolar Lavage Fluid chemistry cytology MeSH
- Chemokine CCL5 genetics metabolism MeSH
- Adult MeSH
- Gene Expression MeSH
- Interferon-gamma genetics metabolism MeSH
- Middle Aged MeSH
- Humans MeSH
- Lymph Nodes metabolism MeSH
- RNA, Messenger metabolism MeSH
- Lung metabolism MeSH
- Sarcoidosis, Pulmonary genetics immunology metabolism MeSH
- T-Box Domain Proteins metabolism MeSH
- Receptors, Chemokine genetics metabolism MeSH
- Receptors, CXCR3 genetics metabolism MeSH
- Receptors, CXCR6 MeSH
- Receptors, Interleukin-2 genetics metabolism MeSH
- Th1 Cells immunology metabolism MeSH
- T-bet Transcription Factor MeSH
- Up-Regulation * MeSH
- Receptors, Virus genetics metabolism MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- CCL5 protein, human MeSH Browser
- Chemokine CCL5 MeSH
- CXCR6 protein, human MeSH Browser
- Interferon-gamma MeSH
- RNA, Messenger MeSH
- T-Box Domain Proteins MeSH
- Receptors, Chemokine MeSH
- Receptors, CXCR3 MeSH
- Receptors, CXCR6 MeSH
- Receptors, Interleukin-2 MeSH
- T-bet Transcription Factor MeSH
- Receptors, Virus MeSH
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.
Eur Respir J. 2012 Jan;39(1):230 PubMed
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