Rheumatism Research Center, Catholic Research Institute of Medical Science, College of Medicine, The Catholic University of Korea, Seoul, 06591, South Korea; Laboratory of Immune Network, Catholic Research Institute of Medical Science, College of Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea; Department of Biomedicine & Health Sciences, College of Medicine, The Catholic University of Korea, 222, Banpo-daero, Seocho-gu, Seoul, 06591, Republic of Korea.
Rheumatism Research Center, Catholic Research Institute of Medical Science, College of Medicine, The Catholic University of Korea, Seoul, 06591, South Korea; Laboratory of Immune Network, Catholic Research Institute of Medical Science, College of Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
J Autoimmun. 2021 May;119:102611. doi: 10.1016/j.jaut.2021.102611. Epub 2021 Feb 22.
Sjögren's syndrome (SS) is an autoimmune disease caused by inflammation of the exocrine gland. The pathological hallmark of SS is the infiltration of lymphocytes into the salivary glands. Increased infiltration of T and B cells into salivary glands exacerbates symptoms of SS. Several recent studies have identified the role of gut microbiota in SS. Butyrate, one of the metabolites of the gut microbiota, regulates T cells; however, its effects on B cells and SS remain unknown. This study determined the therapeutic effect of butyrate on regulating B cells in SS.
Various concentrations of butyrate were intraperitoneally injected three times per week in NOD/ShiLtJ (NOD) mice, the prototype animal model for SS, and observed for more than 10 weeks. Whole salivary flow rate and the histopathology of salivary glands were investigated. Human submandibular gland (HSG) cells and B cells in mouse spleen were used to confirm the anti-inflammatory and immunomodulatory effects of butyrate.
Butyrate increased salivary flow rate in NOD mice and reduced inflammation of salivary gland tissues. It also regulated cell death and the expression of circadian-clock-related genes in HSG cells. Butyrate induced B cell regulation by increasing IL-10-producing B (B10) cells and decreasing IL-17-producing B cells, through the circadian clock genes RAR-related orphan receptor alpha and nuclear receptor subfamily 1 group D member 1.
The findings of this study imply that butyrate may ameliorate SS via reciprocal regulation of IL-10- and IL-17-producing B cells.
干燥综合征（SS）是一种由外分泌腺炎症引起的自身免疫性疾病。SS 的病理特征是淋巴细胞浸润唾液腺。T 细胞和 B 细胞浸润增加会加重 SS 的症状。最近的几项研究已经确定了肠道微生物群在 SS 中的作用。肠道微生物群的代谢物之一丁酸盐调节 T 细胞；然而，其对 B 细胞和 SS 的影响尚不清楚。本研究旨在确定丁酸盐对 SS 中 B 细胞调节的治疗作用。
每周三次通过腹腔内注射不同浓度的丁酸钠，对 SS 的原型动物模型 NOD/ShiLtJ（NOD）小鼠进行注射，并观察了 10 多周。检测全唾液流率和唾液腺组织病理学。使用人下颌下腺（HSG）细胞和小鼠脾脏中的 B 细胞，证实丁酸钠的抗炎和免疫调节作用。
丁酸钠增加了 NOD 小鼠的唾液流量，并减轻了唾液腺组织的炎症。它还通过调节 RAR 相关孤儿受体α和核受体亚家族 1 组 D 成员 1 等昼夜节律基因，调节 HSG 细胞中的细胞死亡和昼夜节律相关基因的表达。丁酸钠通过增加产生白细胞介素 10（IL-10）的 B 细胞（B10）和减少产生白细胞介素 17（IL-17）的 B 细胞来诱导 B 细胞调节。
本研究结果表明，丁酸钠可能通过调节产生白细胞介素 10 和白细胞介素 17 的 B 细胞来改善 SS。
