OBJECTIVES: Behçet's disease (BD) is a multi-systemic inflammatory disease, characterised by recurrent oral aphthosis, genital ulcers, skin lesions and uveitis. We have reported excessive Th1 cell activity in patients with BD. More recently, Th17 cells were suggested to associate with several autoimmune diseases. This study was designed to investigate the role of Th17 related cytokines and signalling molecules in patients with BD. METHODS: We examined mRNA expressions of Th1 and Th17 related cytokines and related signalling molecules in PBMC of 12 patients with BD and 14 normal controls (NC) using quantitative RT-PCR. We studied expressions of the Th17 related cytokines in other four BD patients' skin lesions by immunofluorescence. RESULTS: Major Th17 related cytokines were not detected in unstimulated PBMC in patients with BD. After stimulation, mRNA expressions of TGFβ receptor type 1, IL-12 receptor β2 and suppressor of cytokine signalling protein (SOCS) 1 on PBMC were significantly enhanced in patients with BD, as compared with NC (p<0.05). mRNA expression of RORC, a key transcription factor for Th17 cell differentiation, was comparable between BD and NC. CD4+ T cells infiltrating into BD skin lesion expressed TGFβ1 much more than those infiltrating into non-Behçet's disease erythema nodosum. CONCLUSIONS: These findings suggest that TGFβ/Smad signalling pathway of T cells is overactive in patients with BD.
OBJECTIVES: Behçet's disease (BD) is a multi-systemic inflammatory disease, characterised by recurrent oral aphthosis, genital ulcers, skin lesions and uveitis. We have reported excessive Th1 cell activity in patients with BD. More recently, Th17 cells were suggested to associate with several autoimmune diseases. This study was designed to investigate the role of Th17 related cytokines and signalling molecules in patients with BD. METHODS: We examined mRNA expressions of Th1 and Th17 related cytokines and related signalling molecules in PBMC of 12 patients with BD and 14 normal controls (NC) using quantitative RT-PCR. We studied expressions of the Th17 related cytokines in other four BD patients' skin lesions by immunofluorescence. RESULTS: Major Th17 related cytokines were not detected in unstimulated PBMC in patients with BD. After stimulation, mRNA expressions of TGFβ receptor type 1, IL-12 receptor β2 and suppressor of cytokine signalling protein (SOCS) 1 on PBMC were significantly enhanced in patients with BD, as compared with NC (p<0.05). mRNA expression of RORC, a key transcription factor for Th17 cell differentiation, was comparable between BD and NC. CD4+ T cells infiltrating into BD skin lesion expressed TGFβ1 much more than those infiltrating into non-Behçet's disease erythema nodosum. CONCLUSIONS: These findings suggest that TGFβ/Smad signalling pathway of T cells is overactive in patients with BD.
Authors: Burcu Bakir-Gungor; Elaine F Remmers; Akira Meguro; Nobuhisa Mizuki; Daniel L Kastner; Ahmet Gul; Osman U Sezerman Journal: Eur J Hum Genet Date: 2014-09-17 Impact factor: 4.246