M3 muscarinic acetylcholine receptor–reactive Th17 cells in primary Sjögren’s syndrome

• DOI: 10.1172/jci.insight.135982
• Publication Date: 2020-07-02T16:01:14Z
• Authors: Saori Abe; Hiroto Tsuboi; Hanae Kudo; Hiromitsu Asashima; Yuko Ono; Fumika Honda; Hiroyuki Takahashi; Mizuki Yagishita; Shinya Hagiwara; Yuya Kondo; Isao Matsumoto; Takayuki Sumida
• Keywords: Adult; Male; Receptor, Muscarinic M3; Epitopes, T-Lymphocyte; Middle Aged; Prognosis; Autoantigens; 03 medical and health sciences; Sjogren's Syndrome; 0302 clinical medicine; Case-Control Studies; Humans; Th17 Cells; Female; Aged; Autoantibodies; Follow-Up Studies

M3 muscarinic acetylcholine receptor (M3R) is one of the autoantigens associated with Sjögren's syndrome (SS) and is localized in exocrine glands where disease-specific inflammation occurs. The inflammatory lesion is characterized by infiltration of CD4+ T cells, including clonally expanded Th17 cells. We undertook this study to identify circulating M3R-specific Th17 cells and to determine functional properties of those cells. Using the enzyme-linked immunospot assay (ELISpot) method, we identified M3R-reactive Th17 cells in the peripheral blood of patients with primary SS (pSS). Among 10 examined pSS patients, 10 healthy subjects (HS), and 5 IgG4-related disease (IgG4-RD) patients, M3R-reactive IL-17 secreting cells were significantly increased in 5 pSS patients specifically. The most common T cell epitope, which was analyzed and confirmed by coculture of isolated CD4+ T cells with antigen presenting cells plus M3R peptides in vitro, was peptide 83-95 of M3R. Peptide recognition was partly in an HLA-DR-restricted manner, confirmed by blocking assay. M3R-reactive Th17 cells positivity correlated with higher titers of anti-M3R antibodies, whose systemic disease activity score tended to be higher. Our studies highlight the role of tissue-specific autoantigen-derived circulating Th17 cells in pSS, for which further work might lead to antigen-specific targeted therapy.