a Department of Oral Surgery and Oral Medicine , University of Oslo , Oslo , Norway.
b Department of Clinical Medicine, Gade Laboratory for Pathology , University of Bergen , Bergen , Norway.
Autoimmunity. 2018 May;51(3):135-146. doi: 10.1080/08916934.2018.1446525. Epub 2018 Mar 5.
A characteristic feature of primary Sjögren's syndrome (pSS) is the destruction of salivary and lacrimal glands mediated by mononuclear cell infiltration. Adipocytes can also occupy a large portion of the salivary gland (SG) tissue area, although little is known about their significance in pSS. We have previously investigated adipose tissue infiltration in SG biopsies from pSS patients and non-SS sicca controls. Our findings indicated the distinct incidence of adipose tissue replacement in pSS patients, where adipocytes were detected in interleukin (IL) 6 rich regions. We now aimed to examine the development of adipocytes in the SG microenvironment, and delineate their possible involvement in immune reactions. A microarray analysis was performed on SG from 6 pSS patients and 6 non-SS controls, where the expression levels of genes involved in adipose tissue development, inflammatory responses, and lymphoma development were assessed. Real-time PCR was carried out on SG from 14 pSS patients and 15 non-SS controls to account for IL6, IL10, and IL17 mRNA levels. Immunohistochemical staining of frozen SG tissue using IL17 was also conducted. Our results indicate signalling pathways identified in SG of pSS patients displayed genes leading to prominent adipose tissue development and reduced mitochondrial fatty acid beta-oxidation (ARID5B, OXCT1, BDH1, SOX8, HMGCS2, FTO, ECHS1, PCCA, ACADL and ACADVL), inflammatory responses (IL1R1, IL7R, IL10RA, IL15, IL18RAP, CCL2, CCL5, CCL22, CXCR6, CD14, and CD48), and lymphoma development via JAK-STAT signalling (STAT2, TYK2, EBI3, FAS, TNFRSF1B, MAP3K8, HMOX1, LTB, TNF, STAT1, and BAK1). Genes involved in interferon production and signalling were also detected (IRF1, IRF9, and IRF7), in addition to IL6, IL10, and IL17. Higher mRNA levels of IL6, IL17 and IL10 were observed in the SG of pSS patients compared to controls. Moreover, IL17 positive cells were detected mostly interstitially in the SG and around adipocytes, also within the focal infiltrates. In conclusion, adipocyte development seems to be more prominent in the SG of pSS patients, where adipose tissue replacement is also evident. Whether this is due to disease progression, or the repair process, remains to be investigated. Detection of IL17 positive adipocytes in the target organ suggests their involvement in immune reactions.
原发性干燥综合征（pSS）的一个特征是单核细胞浸润介导的唾液腺和泪腺破坏。脂肪细胞也可以占据唾液腺（SG）组织区域的很大一部分，尽管它们在 pSS 中的意义知之甚少。我们之前研究了 pSS 患者和非 SS 干燥对照组 SG 活检中的脂肪组织浸润。我们的发现表明，pSS 患者中脂肪组织替代的发生率明显不同，在富含白细胞介素（IL）6 的区域检测到脂肪细胞。我们现在旨在研究 SG 微环境中脂肪细胞的发育，并描绘它们在免疫反应中的可能参与。对 6 名 pSS 患者和 6 名非 SS 对照者的 SG 进行了微阵列分析，评估了涉及脂肪组织发育、炎症反应和淋巴瘤发展的基因的表达水平。对 14 名 pSS 患者和 15 名非 SS 对照者的 SG 进行了实时 PCR，以检测 IL6、IL10 和 IL17 mRNA 水平。还使用 IL17 对冷冻 SG 组织进行了免疫组织化学染色。我们的结果表明，在 pSS 患者的 SG 中鉴定出的信号通路显示出导致明显脂肪组织发育和减少线粒体脂肪酸β氧化的基因（ARID5B、OXCT1、BDH1、SOX8、HMGCS2、FTO、ECHS1、PCCA、ACADL 和 ACADVL）、炎症反应（IL1R1、IL7R、IL10RA、IL15、IL18RAP、CCL2、CCL5、CCL22、CXCR6、CD14 和 CD48）以及通过 JAK-STAT 信号传导的淋巴瘤发展（STAT2、TYK2、EBI3、FAS、TNFRSF1B、MAP3K8、HMOX1、LTB、TNF、STAT1 和 BAK1）。还检测到干扰素产生和信号传导涉及的基因（IRF1、IRF9 和 IRF7），以及 IL6、IL10 和 IL17。与对照组相比，pSS 患者的 SG 中观察到更高水平的 IL6、IL17 和 IL10 mRNA。此外，IL17 阳性细胞主要在 SG 间质中、脂肪细胞周围和局灶性浸润中检测到。总之，pSS 患者的 SG 中脂肪细胞的发育似乎更为明显，脂肪组织的替代也很明显。这是由于疾病进展还是修复过程，仍有待研究。在靶器官中检测到 IL17 阳性脂肪细胞表明它们参与免疫反应。
