The role of cytokines and T-bet, GATA3, ROR-γt, and FOXP3 transcription factors of T cell subsets in the natural clinical progression of Type 1 Diabetes.

Th cells play an important role in pathogenesis of type 1 diabetes (T1D). Peripheral blood mononuclear cells were isolated from peripheral blood samples from newly diagnosed (ND), 1-year (1YD), and 5-year T1D (5YD) patients (n:8 of each group), 8 healthy controls (HC), and cultured for 24 h under unstimulated (US) and stimulated conditions. Cell ratios of Th1, Th2, Th17, Treg, and intracellular levels of IFN-γ, TNF-α, IL-10, TGF-β, IL-5, IL-13, IL-17, and IL-21 cytokines were evaluated using the flow cytometry. mRNA expressions of transcription factors T-bet, GATA3, ROR-γt, and FOXP3 of these cells were determined by real-time PCR. Reduced CD4+CD25high cell ratios were detected in ND. CD4+CD25high cells were found to be reduced in ND and 1YD compared to HC under IL-2-stimulated conditions. Intracellular IFN-γ and TNF-α levels were low in all patients under US and IL-12-stimulated conditions. IL-17A and IL-21 were found to be high in patients with IL-6-stimulated conditions. Expressions of IL-10 and TGF-β have been observed to be reduced in patients. Th1/Th2, Th17/Treg, and Th1/Treg ratios were higher in patient groups. FOXP3 and GATA3 mRNA expressions were found to be low in patients, while RORγt and T-bet mRNA levels were higher than HC. Th1, Th17, and Treg cells and their cytokines have been shown to be associated with type 1 diabetes.

Ozgur BA ，Cinar SA ，Coskunpinar E ，Yilmaz A ，Altunkanat D ，Deniz G ，Gurol AO ，Yilmaz MT ... -  《-》

Shenghua Decoction reduces uterine bleeding and regulates T-cell paradigm in human deciduas of RU486 medical abortion.

Excessive uterine bleeding is the most common and problematic side effect of RU486 medical abortion. Shenghua Decoction (SHD) is a well-known traditional Chinese herbal prescription for reducing uterine bleeding induced by RU486 medical abortion. However, its therapeutic mechanism still remains unclear. The Th1/Th2/Th17/Treg paradigm plays an important role in achieving maternal-fetal immunotolerance and its bias participates in RU486-induced abortion. Our previous research on mice demonstrated that the uterine bleeding volume is negatively related to the proportions of Th1 and Th17 cells whereas positively related to the proportions of Th2 and Treg cells. Additionally, Th1-type cytokine inducing effect was identified in our previous study. Therefore, it was hypothesized that SHD reduced the uterine bleeding in RU486 medical abortion by inducing Th1/Th2/Th17/Treg paradigm bias. The purpose of this study was to determine the regulatory effect and the mechanism of SHD on human decidual Th1/Th2/Th17/Treg paradigm for alleviating uterine bleeding in RU486 medical abortion. 90 women within seven weeks of a normal intrauterine pregnancy, who elected for termination of pregnancy, were divided into three groups; vacuum aspiration group, RU486 group, and SHD-RU486 group. Duration of uterine bleeding was recorded and volume of uterine bleeding was measured by the method of alkaline hematin photometric. To determine the regulatory effect of SHD on Th1/Th2/Th17/Treg paradigm, the proportions of Th1/Th2/Th17/Treg cells in the decidua of different groups were analyzed using a FACS calibur. Correlation was analyzed in order to demonstrate the relationship between the Th1/Th2/Th17/Treg paradigm and the uterine bleeding in RU486 medical abortion. Moreover, to elucidate the mechanism underlying the T-cell paradigm regulating of SHD, the mRNA and protein expressions of subset-specific transcription factors (T-bet, GATA-3, RORγt, and Foxp3) for the differentiation of Th1/Th2/Th17/Treg paradigm in human decidual CD4(+) T cells were detected by reverse transcription-polymerase chain reaction (RT-PCR) assay and western blot analysis respectively. Moreover, the mRNA expression of the characteristic cytokines of Th1/Th2/Th17/Treg paradigm (IFNγ, IL-4, IL-17A, TGF-β) were analyzed by RT-PCR assay. Compared with RU486 group, both the uterine bleeding volume and duration reduced significantly in SHD-RU486 group. Both the duration and the volume of the uterine bleeding demonstrated negative correlation with the proportions of Th1 and Th17 cells, whereas showed positive correlation with Th2 and Treg cells. SHD increased the proportions of Th1 and Th17 cells whereas decreased those of Th2 and Treg cells. Thus, the ratios of Th1/Th2 and Th17/Treg cells elevated markedly after SHD treatment. SHD promoted the mRNA as well as the protein expressions of subset-specific transcription factors for the differentiation of Th1 and Th17 subsets (T-bet and RORγt) while inhibited those of Th2 and Treg cells (GATA-3 and Foxp3). Moreover, the mRNA expression of Th1- and Th17- type cytokines (IFNγ and IL-17A) was up-regulated while that of Th2-type and Treg-produced cytokines (IL-4 and TGF-β) was down-regulated significantly after SHD administration. Th1/Th2/Th17/Treg paradigm bias was involved in RU486 medical abortion. SHD reduced the uterine bleeding efficiently by inducing Th1 and Th17 skews in the maternal-fetal of RU486 medical abortion patients. The regulatory effect of SHD on Th1/Th2/Th17/Treg paradigm in RU486 medical abortion is attributed to the modulation of transcription and protein expression of subset-specific transcription factors for T-cell subsets differentiation and their characteristic cytokines.

Li X ，Zhang M ，Wang B ，Li Y ，Wang L ，Zhao X ，Zhou X ，Guo Y ，Jiang G ，Yao C ... -  《-》

The balance between Foxp3 and Ror-γt expression in peripheral blood is altered by tocilizumab and abatacept in patients with rheumatoid arthritis.

Tada Y ，Ono N ，Suematsu R ，Tashiro S ，Sadanaga Y ，Tokuda Y ，Ono Y ，Nakao Y ，Maruyama A ，Ohta A ，Koarada S ... -  《BMC MUSCULOSKELETAL DISORDERS》

Taurohyodeoxycholic acid alleviates trinitrobenzene sulfonic acid induced ulcerative colitis via regulating Th1/Th2 and Th17/Treg cells balance.

Taurohyodeoxycholic acid (THDCA), a natural 6α-hydroxylated bile acid, exhibits intestinal anti-inflammatory effects. This study aimed to explore the efficacy of THDCA on ulcerative colitis and to reveal its mechanisms of action. Colitis was induced by intrarectal administration of trinitrobenzene sulfonic acid (TNBS) to mice. Mice in the treatment group were gavage THDCA (20, 40, and 80 mg/kg/day) or sulfasalazine (500 mg/kg/day) or azathioprine (10 mg/kg/day). The pathologic markers of colitis were comprehensively assessed. The levels of Th1-/Th2-/Th17-/Treg-related inflammatory cytokines and transcription factors were detected by ELISA, RT-PCR, and Western blotting. The balance of Th1/Th2 and Th17/Treg cells was analyzed by Flow cytometry. THDCA significantly alleviated colitis by improving the body weight, colon length, spleen weight, histological characteristics, and MPO activity of colitis mice. THDCA reduced the secretion of Th1-/Th17-related cytokines (IFN-γ, IL-12p70, IL-6, IL-17A, IL-21, IL-22, and TNF-α) and the expressions of transcription factors (T-bet, STAT4, RORγt, and STAT3), but increase the production of Th2-/Treg-related cytokines (IL-4, IL-10, and TGF-β1) and the expressions of transcription factors (GATA3, STAT6, Foxp3, and Smad3) in the colon. Meanwhile, THDCA inhibited the expressions of IFN-γ, IL-17A, T-bet, and RORγt, but improved the expression of IL-4, IL-10, GATA3, and Foxp3 in the spleen. Furthermore, THDCA restored the proportion of Th1, Th2, Th17, and Treg cells, and balanced the Th1/Th2 and Th17/Treg immune response of colitis mice. THDCA can alleviate TNBS-induced colitis via regulating Th1/Th2 and Th17/Treg balance, which may represent a promising treatment for patients with colitis.

Lv L ，Chen Z ，Bai W ，Hao J ，Heng Z ，Meng C ，Wang L ，Luo X ，Wang X ，Cao Y ，He J ... -  《-》

Impact of interleukin-32α on T helper cell-related cytokines, transcription factors, and proliferation in patients with type 2 diabetes mellitus.

Borzouei S ，Gholamian-Hamadan M ，Behzad M 《-》