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Published in: Arthritis Research & Therapy 1/2018

Open Access 01-12-2018 | Research article

The role of RORα in salivary gland lesions in patients with primary Sjögren’s syndrome

Authors: Xiuhong Weng, Yi Liu, Shun Cui, Bo Cheng

Published in: Arthritis Research & Therapy | Issue 1/2018

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Abstract

Background

The orphan nuclear receptors retinoic acid-related receptor α and γt (RORα and RORγt) are critical in the development of T helper 17 (Th17) cells, and ROR-specific synthetic ligands have proven efficacy in several mouse models of autoimmunity. However, the pathological significance of RORα in primary Sjögren’s syndrome (pSS) remains to be elucidated. The present study was designed to clarify the significance of RORα in the pathogenesis of pSS.

Methods

RORα expression in the labial salivary gland (LSG) was determined by immunohistochemical analysis using a quantitative scoring system in 34 patients with pSS. The correlation between RORα expression in LSGs and the focus score (FS) was determined, and Th17 and IL-17 receptor A (1L-17RA) levels in LSGs were determined. To investigate the effect of RORs and the therapeutic potential of targeting RORs in pSS, we administered SR1001, a selective RORα/γt inverse agonist, to non-obese diabetic (NOD) mice.

Results

The expression of RORα was significantly increased in LSGs of patients with pSS and intensified with disease stage/FS, showing a similar increasing trend with IL-17A and IL-17RA. SR1001 significantly improved salivary gland secretory function and relieved sialadenitis in treated mice.

Conclusion

Our data reveal the importance of RORα in controlling pathologic lymphocytic infiltration of the salivary glands and suggest that RORα may be a druggable target in treating pSS.
Appendix
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Metadata
Title
The role of RORα in salivary gland lesions in patients with primary Sjögren’s syndrome
Authors
Xiuhong Weng
Yi Liu
Shun Cui
Bo Cheng
Publication date
01-12-2018
Publisher
BioMed Central
Published in
Arthritis Research & Therapy / Issue 1/2018
Electronic ISSN: 1478-6362
DOI
https://doi.org/10.1186/s13075-018-1698-5

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