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LAMP3 induces apoptosis and autoantigen release in Sjögren's syndrome patients.

Abstract：

:Primary Sjögren's syndrome (pSS) is a complex autoimmune disease characterized by dysfunction of secretory epithelia with only palliative therapy. Patients present with a constellation of symptoms, and the diversity of symptomatic presentation has made it difficult to understand the underlying disease mechanisms. In this study, aggregation of unbiased transcriptome profiling data sets of minor salivary gland biopsies from controls and Sjögren's syndrome patients identified increased expression of lysosome-associated membrane protein 3 (LAMP3/CD208/DC-LAMP) in a subset of Sjögren's syndrome cases. Stratification of patients based on their clinical characteristics suggested an association between increased LAMP3 expression and the presence of serum autoantibodies including anti-Ro/SSA, anti-La/SSB, anti-nuclear antibodies. In vitro studies demonstrated that LAMP3 expression induces epithelial cell dysfunction leading to apoptosis. Interestingly, LAMP3 expression resulted in the accumulation and release of intracellular TRIM21 (one component of SSA), La (SSB), and α-fodrin protein, common autoantigens in Sjögren's syndrome, via extracellular vesicles in an apoptosis-independent mechanism. This study defines a clear role for LAMP3 in the initiation of apoptosis and an independent pathway for the extracellular release of known autoantigens leading to the formation of autoantibodies associated with this disease.ClinicalTrials.gov Identifier: NCT00001196, NCT00001390, NCT02327884.

journal_name

Sci Rep

journal_title

Scientific reports

authors

Tanaka T,Warner BM,Odani T,Ji Y,Mo YQ,Nakamura H,Jang SI,Yin H,Michael DG,Hirata N,Suizu F,Ishigaki S,Oliveira FR,Motta ACF,Ribeiro-Silva A,Rocha EM,Atsumi T,Noguchi M,Chiorini JA

doi

10.1038/s41598-020-71669-5

subject

Has Abstract

pub_date

2020-09-16 00:00:00

pages

15169

issue

1

issn

2045-2322

pii

10.1038/s41598-020-71669-5

journal_volume

10

pub_type

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