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

Saori Abe; Hiroto Tsuboi; Hanae Kudo; Hiromitsu Asashima; Yuko Ono; Fumika Honda; Hiroyuki Takahashi; Mizuki Yagishita; Shinya Hagiwara; Yuya Kondo; Isao Matsumoto; Takayuki Sumida

doi:10.1172/jci.insight.135982

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

Saori Abe,¹ Hiroto Tsuboi,¹ Hanae Kudo,¹ Hiromitsu Asashima,¹ Yuko Ono,¹ Fumika Honda,¹ Hiroyuki Takahashi,¹ Mizuki Yagishita,¹ Shinya Hagiwara,¹ Yuya Kondo,¹ Isao Matsumoto,¹ and Takayuki Sumida¹

Published July 2, 2020 - More info

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Abstract

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 ELISpot method, we identified M3R reactive Th17 cells in the peripheral blood of patients with primary SS (pSS). Among examined 10 pSS, 10 healthy subjects (HS), and 5 IgG4-related disease (IgG4-RD) patients, M3R reactive IL-17 secreting cells were significantly increased in five pSS patients specifically. The commonest T cell epitope, which was analyzed and confirmed by co-culture 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 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.

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

Saori Abe,¹ Hiroto Tsuboi,¹ Hanae Kudo,¹ Hiromitsu Asashima,¹ Yuko Ono,¹ Fumika Honda,¹ Hiroyuki Takahashi,¹ Mizuki Yagishita,¹ Shinya Hagiwara,¹ Yuya Kondo,¹ Isao Matsumoto,¹ and Takayuki Sumida¹

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

Saori Abe,1 Hiroto Tsuboi,1 Hanae Kudo,1 Hiromitsu Asashima,1 Yuko Ono,1 Fumika Honda,1 Hiroyuki Takahashi,1 Mizuki Yagishita,1 Shinya Hagiwara,1 Yuya Kondo,1 Isao Matsumoto,1 and Takayuki Sumida1

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Saori Abe,¹ Hiroto Tsuboi,¹ Hanae Kudo,¹ Hiromitsu Asashima,¹ Yuko Ono,¹ Fumika Honda,¹ Hiroyuki Takahashi,¹ Mizuki Yagishita,¹ Shinya Hagiwara,¹ Yuya Kondo,¹ Isao Matsumoto,¹ and Takayuki Sumida¹