The interferon-gamma (IFN-γ)-inducible chemotactic cytokines (chemokines), CXCL9 and CXCL10, are both increased in sarcoidosis patients, yet they possess important molecular differences.
In addition, IL-17/IFNγ double-producing cells have been identified in disorders in which the role of autoimmunity remains unclear, such as sarcoidosis.
This finding was also observed in vimentin stimulation of sarcoidosis PBMCs compared to PBMCs from healthy controls (IFN-γ: 396.6 pg/mL vs. 0.1 pg/mL, p = 0.014; TNF-α: 1139 pg/mL vs 42.29 pg/mL, p = 0.027).
Strikingly, all these transcriptomics data confirm the key role of TH1 immune response in sarcoidosis and particularly of interferon-γ (IFN-γ) and type I IFN-driven signaling pathways.
Although the knowledge on the molecular background of sarcoidosis is limited, it seems that the important pathways involve transforming growth factor-β (TGF-β) and JAK/STAT, which may influence the interferon-γ (IFN-γ)-mediated signaling.
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.
We have screened for mutations in the cystic fibrosis conductance regulator (CFTR) gene and genotyped single-nucleotide polymorphisms in the tumor necrosis factor (TNF), interferon alpha-10 (IFNA10), IFNA17, and interferon gamma (IFNG) genes in 89 Greek patients with sarcoidosis and 212 control subjects to detect possible association between them and the risk for developing sarcoidosis.
[Interferon gamma (IFN-gamma) level in broncholaveolar lavage (BAL) fluid is positively correlated with CD4/CD8 ratio in selected interstitial lung diseases].
These novel results indicate that IFN-gamma represses PPARgamma in human alveolar macrophages but that in sarcoidosis, PPARgamma rather than IFN-gamma levels correlate best with disease severity.
Depressed peroxisome proliferator-activated receptor gamma (PPargamma) is indicative of severe pulmonary sarcoidosis: possible involvement of interferon gamma (IFN-gamma).
In the present study, short tandem repeats (STR) polymorphism within the first intron of IFN-gamma gene in connection with HLA-DRB1*03 specificities was analysed in 43 sarcoidosis patients, 14 of which presented with Löfgren's syndrome (LS).
Our results coupled with those of previous investigations demonstrating activity of IL-18 in inducing interferon-gamma production suggest a significant role of IL-18 in the pathogenesis of sarcoidosis.
These results are consistent with previous observations of a paucity of INFgamma and a predominantly type II (Th2-like) pattern of immune response in patients with CFA and suggest a possible imbalance of pro-fibrogenic cytokines in the distal lung of patients with this condition, compared with those with EAA or sarcoid.
Cytokines released by T lymphocytes activated in the course of sarcoidosis, e.g., interleukin-2 (IL-2) and interferon-gamma (IFN-gamma), indicate the presence of Th1 cells leading to the question of Th1/Th0/Th2 balance in sarcoidosis.
In addition, these data implicate an elevated expression of interleukin-2, -10 and -12 and interferon-gamma in active compared to nonactive sarcoidosis.