Signalling pathways identified in salivary glands from primary Sjögren’s syndrome patients reveal enhanced adipose tissue development
Creators: name: Aqrawi, Lara A.
name: Janicke Liaaen Jensen
name: Øijordsbakken, Gunnvor
name: Ann-Kristin Ruus
name: Nygård, Ståle
name: Holden, Marit
name: Jonsson, Roland
name: Galtung, Hilde Kanli
name: Skarstein, Kathrine
Publisher: name: Taylor & Francis
Year: 2018
Subjects: subject: Biochemistry
subject: Medicine
subject: Cell Biology
subject: Genetics
subject: FOS: Biological sciences
subject: FOS: Biological sciences
subject: Molecular Biology
subject: Physiology
subject: 39999 Chemical Sciences not elsewhere classified
subject: FOS: Chemical sciences
subject: FOS: Chemical sciences
subject: Immunology
subject: FOS: Clinical medicine
subject: FOS: Clinical medicine
subject: 69999 Biological Sciences not elsewhere classified
subject: Developmental Biology

description: 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 (<i>ARID5B</i>, <i>OXCT1</i>, <i>BDH1</i>, <i>SOX8</i>, <i>HMGCS2</i>, <i>FTO</i>, <i>ECHS1</i>, <i>PCCA</i>, <i>ACADL</i> and <i>ACADVL</i>), inflammatory responses (<i>IL1R1, IL7R, IL10RA, IL15, IL18RAP, CCL2, CCL5, CCL22, CXCR6, CD14</i>, and <i>CD48</i>), and lymphoma development via JAK-STAT signalling (<i>STAT2, TYK2, EBI3, FAS, TNFRSF1B, MAP3K8, HMOX1, LTB, TNF, STAT1,</i> and <i>BAK1</i>). Genes involved in interferon production and signalling were also detected (<i>IRF1, IRF9,</i> and <i>IRF7</i>), in addition to <i>IL6, IL10</i>, and <i>IL17</i>. 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.