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RESEARCH PRODUCT

CD4 T lymphocyte autophagy is upregulated in the salivary glands of primary Sjögren’s syndrome patients and correlates with focus score and disease activity

Aroldo RizzoE. AstorriAntonina MinnitiAnnacarla FinucciTania ColasantiGiuliana GugginoCristiano AlessandriRiccardo AlessandroFrancesco CicciaMarina PierdominiciWalter MalorniGiovanni TrioloGuido ValesiniMarta VomeroCristiana BarbatiFabrizio ContiRoberta PrioriM. PendolinoElena Ortona

subject

AdultCD4-Positive T-LymphocytesMale0301 basic medicinePathologymedicine.medical_specialtylcsh:Diseases of the musculoskeletal systemAutophagy; Cytokines; Lymphocytes; Sjögren syndrome; Immunology and Allergy; Rheumatology; ImmunologyLymphocyteImmunologySjögren syndromeSalivary GlandsPathogenesis03 medical and health sciencesImmune systemRheumatologystomatognathic systemSicca syndromeAutophagymedicineImmunology and AllergyHumansLymphocytesCytokineAgedSjögren syndrome; Autophagy; Lymphocytes; CytokinesAutoimmune diseaseSalivary glandbusiness.industryAutophagyT lymphocyteMiddle Agedmedicine.diseaseSjögren syndromeUp-RegulationSettore MED/16 - Reumatologiastomatognathic diseasesSjogren's Syndrome030104 developmental biologymedicine.anatomical_structureImmunologyCytokinesLymphocyteFemalelcsh:RC925-935businessResearch Article

description

Background Primary Sjögren’s syndrome (pSS) is a common chronic autoimmune disease characterized by lymphocytic infiltration of exocrine glands and peripheral lymphocyte perturbation. In the current study, we aimed to investigate the possible pathogenic implication of autophagy in T lymphocytes in patients with pSS. Methods Thirty consecutive pSS patients were recruited together with 20 patients affected by sicca syndrome and/or chronic sialoadenitis and 30 healthy controls. Disease activity and damage were evaluated according to SS disease activity index, EULAR SS disease activity index, and SS disease damage index. T lymphocytes were analyzed for the expression of autophagy-specific markers by biochemical, molecular, and histological assays in peripheral blood and labial gland biopsies. Serum interleukin (IL)-23 and IL-21 levels were quantified by enzyme-linked immunosorbent assay. Results Our study provides evidence for the first time that autophagy is upregulated in CD4+ T lymphocyte salivary glands from pSS patients. Furthermore, a statistically significant correlation was detected between lymphocyte autophagy levels, disease activity, and damage indexes. We also found a positive correlation between autophagy enhancement and the increased salivary gland expression of IL-21 and IL-23, providing a further link between innate and adaptive immune responses in pSS. Conclusions These findings suggest that CD4+ T lymphocyte autophagy could play a key role in pSS pathogenesis. Additionally, our data highlight the potential exploitation of T cell autophagy as a biomarker of disease activity and provide new ground to verify the therapeutic implications of autophagy as an innovative drug target in pSS. Electronic supplementary material The online version of this article (doi:10.1186/s13075-017-1385-y) contains supplementary material, which is available to authorized users.

https://doi.org/10.1186/s13075-017-1385-y