Short-Chain Fatty Acids Promote Immunotherapy by Modulating Immune Regulatory Property in B Cells.
Short-Chain Fatty Acids Promote Immunotherapy by Modulating Immune Regulatory Property in B Cells.
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短链脂肪酸通过调节 B 细胞的免疫调节特性促进免疫治疗
DOI：
10.1155/2021/2684361
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发表时间：
2021
影响因子：
4.1
通讯作者：
Yang PC
中科院分区：
文献类型：
--
作者：
Zhou CJ;Xie BL;Han HY;Wang Y;Wang YH;Hong JY;Wei YX;Liu ZG;Feng Y;Yang G;Yang PC
调节性B细胞（Breg）功能失调可能导致诸如过敏性鼻炎（AR）等免疫炎症；其潜在机制尚未完全明确。短链脂肪酸，如丙酸（PA），具有免疫调节功能。本研究旨在验证一个假说，即调节PA的产生可通过维持Breg功能来缓解气道过敏。从过敏性鼻炎患者和健康对照（HC）受试者的血液中分离出B细胞。采用实时定量聚合酶链反应（RT - qPCR）检测B细胞中白细胞介素 - 10（IL - 10）mRNA的稳定性。建立过敏性鼻炎小鼠模型以检测PA在稳定B细胞中IL - 10表达的作用。我们发现过敏性鼻炎患者血清中PA水平与血清Th2细胞因子水平呈负相关。过敏性鼻炎患者血清PA水平与外周CD5⁺B细胞频率呈正相关；CD5⁺B细胞也表达IL - 10。在B细胞中观察到IL - 10 mRNA的自发降解，PA通过激活GPR43可阻止这种降解。PA通过AKT/T - bet/颗粒酶B途径抵消了三核苷酸重复序列结合蛋白（TTP）诱导B细胞中IL - 10 mRNA降解的作用。玉屏风散（一种中药方剂）或吲哚 - 3 - 丙酸给药可诱导肠道细菌产生PA，从而稳定B细胞中IL - 10的表达，促进过敏原特异性免疫治疗，并有效缓解实验性过敏性鼻炎。总之，数据表明CD5⁺B细胞产生IL - 10。过敏性鼻炎患者血清中PA水平较低与CD5⁺B细胞频率较低有关。玉屏风散或吲哚 - 3 - 丙酸给药可改善Breg功能并缓解实验性过敏性鼻炎。
The dysfunction of regulatory B cells (Breg) may result in immune inflammation such as allergic rhinitis (AR); the underlying mechanism is not fully understood yet. Short-chain fatty acids, such as propionic acid (PA), have immune regulatory functions. This study is aimed at testing a hypothesis that modulates PA production alleviating airway allergy through maintaining Breg functions. B cells were isolated from the blood obtained from AR patients and healthy control (HC) subjects. The stabilization of IL-10 mRNA in B cells was tested with RT-qPCR. An AR mouse model was developed to test the role of PA in stabilizing the IL-10 expression in B cells. We found that the serum PA levels were negatively correlated with the serum Th2 cytokine levels in AR patients. Serum PA levels were positively associated with peripheral CD5+ B cell frequency in AR patients; the CD5+ B cells were also IL-10+. The spontaneous IL-10 mRNA decay was observed in B cells, which was prevented by the presence of PA through activating GPR43. PA counteracted the effects of Tristetraprolin (TTP) on inducing IL-10 mRNA decay in B cells through the AKT/T-bet/granzyme B pathway. Administration of Yupinfeng San, a Chinese traditional medical formula, or indole-3-PA, induced PA production by intestinal bacteria to stabilize the IL-10 expression in B cells, which promoted the allergen specific immunotherapy, and efficiently alleviated experimental AR. In summary, the data show that CD5+ B cells produce IL-10. The serum lower PA levels are associated with the lower frequency of CD5+ B cells in AR patients. Administration with Yupinfeng San or indole-3-PA can improve Breg functions and alleviate experimental AR.