School of Bioscience, IIT Kharagpur, Kharagpur, 721302, West Bengal, India.
Department of Orthopedic Surgery, King George's Medical University, Lucknow, Uttar Pradesh, 226003, India.
Mol Cell Biochem. 2021 Jan;476(1):369-384. doi: 10.1007/s11010-020-03914-4. Epub 2020 Sep 23.
There is limited information regarding the TLR2 signaling pathway involved in Th9 cell differentiation. The role of calcitriol in regulating TLR2-mediated Th9 cell development is unknown. Thus, we aimed to unravel the TLR2 signaling pathway in Th9 cells and its regulation by calcitriol. We have used n = 5-6 animals for each murine experiment. Human studies involved five healthy volunteers. Moreover, ten healthy individuals and ten RA patients were included in the study. Murine and human Th9 cells were treated with Calcitriol (100 nM) and PamCSK (2 µg/mL). The number of IL-9+ve cells was determined by flow cytometry. Real-time PCR was used to assess the gene expression. Serum 25(OH)D levels were determined by HPLC. We observed that TLR2 signals via IL-33/ST2 in Th9 cells. Increased TLR2 expression associated with increased IL9 expression and augmented disease severity in RA patients. Calcitriol attenuated TLR2 signaling in murine and human Th9 cells. Low serum vitamin D3 level negatively associated with increased IL-9 and TLR2 expression and disease severity in RA patients. Our data suggest a potential role of calcitriol to ameliorate the disease severity of RA patients.
关于参与 Th9 细胞分化的 TLR2 信号通路的信息有限。骨化三醇在调节 TLR2 介导的 Th9 细胞发育中的作用尚不清楚。因此，我们旨在揭示 Th9 细胞中的 TLR2 信号通路及其被骨化三醇的调节。我们对每个鼠实验使用了 n = 5-6 只动物。人类研究涉及五名健康志愿者。此外，研究还纳入了十名健康个体和十名 RA 患者。用骨化三醇（100 nM）和 PamCSK（2 µg/mL）处理鼠和人 Th9 细胞。通过流式细胞术测定 IL-9+ve 细胞的数量。实时 PCR 用于评估基因表达。用 HPLC 测定血清 25(OH)D 水平。我们观察到 TLR2 通过 Th9 细胞中的 IL-33/ST2 发出信号。TLR2 表达增加与 RA 患者 IL9 表达增加和疾病严重程度增加相关。骨化三醇减弱了鼠和人 Th9 细胞中的 TLR2 信号。血清维生素 D3 水平低与 RA 患者 IL-9 和 TLR2 表达增加以及疾病严重程度呈负相关。我们的数据表明骨化三醇可能具有改善 RA 患者疾病严重程度的作用。
