The Rheumatism Research Center, Catholic Research Institute of Medical Science, College of Medicine, The Catholic University of Korea, Seoul, South Korea.
Department of Biomedicine & Health Sciences, College of Medicine, The Catholic University of Korea, Seoul, South Korea.
Front Immunol. 2021 Sep 1;12:721453. doi: 10.3389/fimmu.2021.721453. eCollection 2021.
Previous studies have evaluated the roles of T and B cells in the pathogenesis of Sjögren's syndrome (SS); however, their relationships with age-dependent and metabolic abnormalities remain unclear. We examined the impacts of changes associated with aging or metabolic abnormalities on populations of T and B cells and SS disease severity. We detected increased populations of IL-17-producing T and B cells, which regulate inflammation, in the salivary glands of NOD/ShiLtJ mice. Inflammation-induced human submandibular gland cell death, determined based on p-MLKL and RIPK3 expression levels, was significantly increased by IL-17 treatment. Among IL-17-expressing cells in the salivary gland, peripheral blood, and spleen, the α4β7 (gut-homing integrin)-negative population was significantly increased in aged NOD/ShiLtJ mice. The α4β7-positive population markedly increased in the intestines of aged NOD/ShiLtJ mice following retinoic acid (RA) treatment. A significant increase in α4β7-negative IL-17-expressing cells in salivary glands may be involved in the onset and progression of SS. These results suggest the potential therapeutic utility of RA in SS treatment.
先前的研究已经评估了 T 细胞和 B 细胞在干燥综合征 (SS) 发病机制中的作用；然而，它们与年龄相关和代谢异常的关系尚不清楚。我们研究了与衰老或代谢异常相关的变化对 T 细胞和 B 细胞群体以及 SS 疾病严重程度的影响。我们在 NOD/ShiLtJ 小鼠的唾液腺中检测到了更多的产生白细胞介素-17 (IL-17) 的 T 细胞和 B 细胞，这些细胞调节炎症。根据 p-MLKL 和 RIPK3 表达水平，IL-17 处理显著增加了炎症诱导的人下颌下腺细胞死亡。在唾液腺、外周血和脾脏中表达 IL-17 的细胞中，在衰老的 NOD/ShiLtJ 小鼠中，α4β7（肠道归巢整合素）阴性群体显著增加。在视黄酸 (RA) 治疗后，衰老的 NOD/ShiLtJ 小鼠的肠道中α4β7 阳性群体明显增加。唾液腺中 α4β7 阴性 IL-17 表达细胞的显著增加可能与 SS 的发病和进展有关。这些结果表明 RA 在 SS 治疗中的潜在治疗效用。
