Abstract
BackgroundPrimary 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.MethodsThirty 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.ResultsOur 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.ConclusionsThese 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.
Highlights
Primary Sjögren’s syndrome is a common chronic autoimmune disease characterized by lymphocytic infiltration of exocrine glands and peripheral lymphocyte perturbation
Sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) and Western blot To evaluate whether autophagy was detectable in freshly isolated peripheral T lymphocytes of Primary Sjögren’s syndrome (pSS) patients, we examined the expression of an established set of autophagosomal markers: Protein light-chain 3 (LC3)-II, p62/SQSTM1, and Atg5 [29]
These findings suggest a general state of activation within circulating T cells in the disease population
Summary
Primary Sjögren’s syndrome (pSS) is a common chronic autoimmune disease characterized by lymphocytic infiltration of exocrine glands and peripheral lymphocyte perturbation. Primary Sjögren’s syndrome (pSS) is a systemic autoimmune disease characterized by infiltration of exocrine glands by T and B lymphocytes that, by producing chemokines and cytokines, play a fundamental role in coordinating the chronic inflammatory process [1, 2]. Other different genes and proteins finely regulate the autophagy process, among them: ATG16L1, the main component of a large protein complex essential for autophagy; the immunity-associated GTPase family M (IRGM), which regulates autophagy formation in response to intracellular pathogens; ATG5, a ubiquitin ligase essential for autophagosomal elongation; HSPA8/HSC70, a protein that binds to nascent polypeptides to facilitate correct protein folding; HSP90AA1, involved in the proper folding of specific target proteins; p62/SQSTM1, a protein that links ubiquitinated proteins to the autophagic machinery to enable their degradation [12]
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