T-helper cell type-1 transcription factor T-bet is upregulated in pulmonary sarcoidosis

Eur Respir J. 2011 Nov;38(5):1136-44. doi: 10.1183/09031936.00089910. Epub 2011 May 3.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Bronchoalveolar Lavage Fluid / chemistry
  • Bronchoalveolar Lavage Fluid / cytology
  • Chemokine CCL5 / genetics
  • Chemokine CCL5 / metabolism
  • Female
  • Gene Expression
  • Humans
  • Interferon-gamma / genetics
  • Interferon-gamma / metabolism
  • Lung / metabolism
  • Lymph Nodes / metabolism
  • Male
  • Middle Aged
  • RNA, Messenger / metabolism
  • Receptors, CXCR3 / genetics
  • Receptors, CXCR3 / metabolism
  • Receptors, CXCR6
  • Receptors, Chemokine / genetics
  • Receptors, Chemokine / metabolism
  • Receptors, Interleukin-2 / genetics
  • Receptors, Interleukin-2 / metabolism
  • Receptors, Virus / genetics
  • Receptors, Virus / metabolism
  • Sarcoidosis, Pulmonary / genetics
  • Sarcoidosis, Pulmonary / immunology
  • Sarcoidosis, Pulmonary / metabolism*
  • T-Box Domain Proteins / metabolism*
  • Th1 Cells / immunology
  • Th1 Cells / metabolism*
  • Up-Regulation*


  • CCL5 protein, human
  • CXCR6 protein, human
  • Chemokine CCL5
  • RNA, Messenger
  • Receptors, CXCR3
  • Receptors, CXCR6
  • Receptors, Chemokine
  • Receptors, Interleukin-2
  • Receptors, Virus
  • T-Box Domain Proteins
  • T-box transcription factor TBX21
  • Interferon-gamma