Affiliated ENT Hospital of Shenzhen University School of Medicine and Longgang ENT Hospital & Shenzhen ENT Institute, Shenzhen, China; Research Center of Allergy & Immunology, Shenzhen University School of Medicine. Shenzhen, China.
Affiliated ENT Hospital of Shenzhen University School of Medicine and Longgang ENT Hospital & Shenzhen ENT Institute, Shenzhen, China; Research Center of Allergy & Immunology, Shenzhen University School of Medicine. Shenzhen, China; Brain-Body Institute, McMaster University, Hamilton, ON, Canada.
Immunobiology. 2019 Nov;224(6):804-810. doi: 10.1016/j.imbio.2019.08.006. Epub 2019 Aug 23.
The immune regulatory cell dysfunction is associated with many immune diseases including food allergy (FA). This study aims to investigate the role of vasoactive intestinal peptide (VIP) in the maintenance of regulatory B cell (Br cell)'s immune suppressive functions by stabilizing thrombospondin (TSP1) expression. In this study, blood samples were collected from patients with food allergy (FA) and healthy control (HC) subjects. Br cells were isolated from the samples through flow cytometry cell sorting and analyzed by immunological approaches to determine the immune regulatory capacity. We found that the immune suppressive functions of Br cells were impaired in FA patients. The serum VIP levels were associated with the production of immune suppressive function-related mediators (interleukin-10, IL-10) of Br cells in FA patients. VIP counteracted IL-10 mRNA decay in Br cells by up regulating the TSP1 expression. TSP1 inhibited tristetraprolin (TTP) to prevent IL-10 mRNA decay in Br cells. Administration of VIP inhibited FA response through restoration of immune suppressive functions in Br cells. In conclusion, administration of VIP can alleviate FA response through up regulating expression of TSP1 to stabilize IL-10 expression in FA Br cells and recover the immune regulatory functions. The results have translational potential for the treatment of FA and other disorders associated with immune regulatory dysfunction of Br cells.
免疫调节细胞功能障碍与许多免疫疾病有关，包括食物过敏（FA）。本研究旨在通过稳定血小板反应蛋白 1（TSP1）的表达来研究血管活性肠肽（VIP）在维持调节性 B 细胞（Br 细胞）免疫抑制功能中的作用。本研究收集了食物过敏（FA）患者和健康对照（HC）受试者的血液样本。通过流式细胞术分选从样本中分离 Br 细胞，并通过免疫学方法进行分析，以确定免疫调节能力。我们发现 FA 患者 Br 细胞的免疫抑制功能受损。FA 患者 Br 细胞产生免疫抑制功能相关介质（白细胞介素 10，IL-10）的血清 VIP 水平与 Br 细胞中 VIP 的产生有关。VIP 通过上调 TSP1 的表达来拮抗 Br 细胞中 IL-10 mRNA 的降解。TSP1 抑制三丝氨酸蛋白磷酸酶 1（TTP）以防止 Br 细胞中 IL-10 mRNA 的降解。VIP 的给药通过恢复 Br 细胞中的免疫抑制功能来抑制 FA 反应。总之，通过上调 TSP1 的表达来稳定 FA Br 细胞中 IL-10 的表达并恢复免疫调节功能，VIP 的给药可以减轻 FA 反应。该结果对于治疗 FA 和其他与 Br 细胞免疫调节功能障碍相关的疾病具有转化潜力。
