Expression profiling of Th17 cell activators revealed elevation of STAT-3 in progressing sarcoidosis
R. Fillerova, E. Kriegova, T. Tomankova, F. Mrazek, M. Zurkova, V. Kolek, M. Petrek (Olomouc, Czech Republic)
Source: Annual Congress 2011 - Bronchoalveolar lavage and biomarkers in diffuse parenchymal lung disease
Disease area: Interstitial lung diseases
Abstract Sarcoidosis is a Th1/Th17 multisystem inflammatory disorder of unknown aetiology. Although Th17 cells have been implicated in sarcoidosis and its progression, there is limited information about the molecules involved in the Th17 immune response in sarcoidosis and its phenotypes. We, therefore, investigated, mRNA expression of Th17 pathway activators (IL-6, IL-21, IL-23, TGFbeta, RORC, STAT-3) together with the cytokines produced by Th17 cells (IL-17A, IL-17F, IL-22) by quantitative RT-PCR in bronchoalveolar (BAL) cells from 77 sarcoidosis patients (S) and 20 control subjects (C); subanalysis was performed in sarcoid phenotypes. Of studied Th17 activators, IL-6 (mean S/C; 0.37/0.04, p =0.0001), IL-21 (0.002/0.001, p =0.001), IL-23 (0.06/0.02, p =0.001), TGFbeta (0.86/0.51, p =0.02) and RORC (0.06/0.02, p =0.0002) were up-regulated in sarcoidosis vs. controls. Expression of Th17 cytokines did not differ between sarcoidosis and controls (p> 0.05). The expression profiling in remitting (n=27) and progressing (n=40) sarcoidosis, as assessed by the disease outcome after 2 years, revealed elevation of STAT-3 in progressing sarcoidosis (p =0.01). In conclusion, increased expression of Th17 activators (IL-6, IL-21, IL-23, TGFbeta, RORC) was observed in sarcoid BAL cells irrespective of clinical phenotype. Enhanced expression of STAT-3, an essential regulator of Th17 cells, was detected in patients with progressing sarcoidosis. Further studies on the role of STAT-3 and Th17 cells in the progression towards the fibrosis in sarcoidosis are needed. Grant support: IGA MZ CR NS/11117, IGA MZ CR NS/10267, PU LF_2010_008.
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R. Fillerova, E. Kriegova, T. Tomankova, F. Mrazek, M. Zurkova, V. Kolek, M. Petrek (Olomouc, Czech Republic). Expression profiling of Th17 cell activators revealed elevation of STAT-3 in progressing sarcoidosis. Eur Respir J 2011; 38: Suppl. 55, 4762
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