Department of Otolaryngology, Head & Neck Surgery, The Second Hospital, Shanxi Medical University, Taiyuan, China.
The Research Center of Allergy & Immunology, Shenzhen University School of Medicine, Shenzhen, China.
Allergy. 2017 Nov;72(11):1704-1712. doi: 10.1111/all.13186. Epub 2017 May 23.
The function of interleukin (IL)-10-producing B cells (B10 cell) is compromised in patients with allergic diseases. Protease-activated receptor (PAR)-2 has immunoregulatory functions. This study aimed to elucidate the role of PAR2 in the suppression of IL-10 expression in peripheral B cells.
Peripheral blood B cells were collected from patients with allergic rhinitis (AR). A correlation between the expression of Bcl2-like protein 12 (Bcl2L12) and IL-10 in the B cells was analyzed. An AR mouse model was developed.
We observed that the expression of IL-10 was lower in the peripheral B cells from patients with airway allergy. A negative correlation was identified between the expression of IL-10 and PAR2 in B cells. Activation of PAR2 of B cells increased the expression of Bcl2L12 and suppression of LPS-induced IL-10 expression, which were inhibited by knocking down the Bcl2L12 gene. Treating B cells from AR patients with Bcl2L12-shRNA-carrying liposomes reversed the capability of IL-10 expression and the immunosuppressive function. Administration of Bcl2L12 shRNA-carrying liposomes attenuated experimental AR in mice.
Activation of PAR2 inhibits the expression of IL-10 in B cells, which can be reversed by treating B cells with Bcl2L12 shRNA-carrying liposomes. The data suggest that regulation of Bcl2L12 may be a novel approach in the treatment for AR.
白细胞介素 (IL)-10 产生 B 细胞（B10 细胞）的功能在过敏疾病患者中受损。蛋白酶激活受体 (PAR)-2 具有免疫调节功能。本研究旨在阐明 PAR2 在抑制外周 B 细胞中 IL-10 表达中的作用。
从过敏性鼻炎 (AR) 患者中采集外周血 B 细胞。分析 B 细胞中 Bcl2 样蛋白 12 (Bcl2L12) 和 IL-10 的表达之间的相关性。建立 AR 小鼠模型。
我们观察到气道过敏患者外周 B 细胞中 IL-10 的表达较低。B 细胞中 PAR2 的表达与 IL-10 呈负相关。B 细胞 PAR2 的激活增加了 Bcl2L12 的表达，并抑制了 LPS 诱导的 IL-10 表达，而敲低 Bcl2L12 基因则抑制了这种作用。用携带 Bcl2L12-shRNA 的脂质体处理 AR 患者的 B 细胞，逆转了 IL-10 表达和免疫抑制功能。给予携带 Bcl2L12-shRNA 的脂质体可减轻小鼠实验性 AR。
PAR2 的激活抑制了 B 细胞中 IL-10 的表达，而用携带 Bcl2L12-shRNA 的脂质体处理 B 细胞可逆转这一作用。数据表明，调节 Bcl2L12 可能是治疗 AR 的一种新方法。
