Department of Otolaryngology-Head and Neck Surgery, University of Missouri, Columbia, MO, USA; Department of Bond Life Sciences Center, University of Missouri, Columbia, MO, USA.
School of Dentistry and Department of Dermatology, University of Utah, Salt Lake City, UT, USA.
Ann Diagn Pathol. 2022 Feb;56:151865. doi: 10.1016/j.anndiagpath.2021.151865. Epub 2021 Nov 17.
Our previous studies demonstrated that resolvin D1 (RvD1) and its aspirin-trigged (AT) form AT-RvD1, are effective in decreasing inflammation while restoring saliva flow rates in a Sjögren's syndrome (SS)-like mouse model before and after disease onset. Resolvins are specialized pro-resolving mediators (SPM) that actively regulate inflammation. However, we only have extensive data within the salivary glands for RvD1 and AT-RvD1, both of which bind to the receptor ALX/FPR2. As such, the presence of other SPM receptors is unknown within salivary glands. Therefore, the goal of this study was to determine the expression of SPM receptors in non-SS and SS patients. For this purpose, six human minor salivary glands from female subjects were analyzed by H&E using the Chisholm and Mason classification to determine the degree of lymphocytic infiltration. Next, confocal immunofluorescence analysis was performed to determine the presence and distribution of different SPM receptors in mucous acini and striated ducts. We observed diffuse presence of lymphocytic infiltration and clinical data were consistent with SS diagnosis in three patients. Moreover, confocal immunofluorescence analysis indicated the presence of the receptors ALX/FPR2, BLT1 and CMKLR1 in the mucous acini and striated ducts of both non-SS and SS patients. GPR32 was absent in SS and non-SS minor salivary glands. In summary, our results showed that various SPM receptors are expressed in non-SS and SS minor salivary glands, all of which may pose as potential targets for promoting pro-epithelial and anti-inflammatory/pro-resolution signaling on SS patients.
我们之前的研究表明,解析素 D1(RvD1)及其阿司匹林触发(AT)形式 AT-RvD1,在疾病发生前后的干燥综合征(SS)样小鼠模型中,可有效减少炎症同时恢复唾液流量。解析素是专门的促解决介质(SPM),可积极调节炎症。然而,我们仅在唾液腺中具有 RvD1 和 AT-RvD1 的广泛数据,这两者都与受体 ALX/FPR2 结合。因此,在唾液腺中其他 SPM 受体的存在尚不清楚。因此,本研究的目的是确定 SPM 受体在非 SS 和 SS 患者中的表达。为此,使用 Chisholm 和 Mason 分类法通过 H&E 分析了 6 名女性受试者的 6 个人体小唾液腺,以确定淋巴细胞浸润的程度。接下来,进行共聚焦免疫荧光分析以确定不同 SPM 受体在黏液腺和纹状导管中的存在和分布。我们观察到三个患者均存在弥漫性淋巴细胞浸润,临床数据与 SS 诊断一致。此外,共聚焦免疫荧光分析表明,在非 SS 和 SS 患者的黏液腺和纹状导管中均存在受体 ALX/FPR2、BLT1 和 CMKLR1。GPR32 在 SS 和非 SS 小唾液腺中均不存在。总之,我们的结果表明,各种 SPM 受体在非 SS 和 SS 小唾液腺中表达,所有这些受体都可能成为促进 SS 患者上皮促愈和抗炎/促解决信号的潜在靶标。