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Aged Sanroque Mice Spontaneously Develop Sjögren's Syndrome-like Disease

  • Suk San Choi (Laboratory of Autoimmunology, Department of Anatomy and Cell Biology, Hanyang University College of Medicine) ;
  • Eunkyeong Jang (Laboratory of Autoimmunology, Department of Anatomy and Cell Biology, Hanyang University College of Medicine) ;
  • Yeon-Kyung Oh (Laboratory of Autoimmunology, Department of Anatomy and Cell Biology, Hanyang University College of Medicine) ;
  • Kiseok Jang (Department of Pathology, Hanyang University College of Medicine) ;
  • Mi-La Cho (Department of Medical Life Science, College of Medicine, The Catholic University of Korea) ;
  • Sung-Hwan Park (Division of Rheumatology, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea) ;
  • Jeehee Youn (Laboratory of Autoimmunology, Department of Anatomy and Cell Biology, Hanyang University College of Medicine)
  • Received : 2018.10.20
  • Accepted : 2019.01.29
  • Published : 2019.02.28
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Abstract

Sjögren's syndrome (SS) is a chronic inflammatory autoimmune disorder that affects mainly salivary and lacrimal glands, but its cause remains largely unknown. Clinical data indicating that SS occurs in a substantial proportion of patients with lupus points to common pathogenic mechanisms underlying the two diseases. To address this idea, we asked whether SS develops in the lupus-prone mouse strain sanroque (SAN). Owing to hyper-activation of follicular helper T (Tfh) cells, female SAN mice developed lupus-like symptoms at approximately 20 wk of age but there were no signs of SS at that time. However, symptoms typical of SS were evident at approximately 40 wk of age, as judged by reduced saliva flow rate, sialadenitis, and IgG deposits in the salivary glands. Increases in serum titers of SS-related autoantibodies and numbers of autoantibody-secreting cells in cervical lymph nodes (LNs) preceded the pathologic manifestations of SS and were accompanied by expansion of Tfh cells and their downstream effector cells. Thus, our results suggest that chronic dysregulation of Tfh cells in salivary gland-draining LNs is sufficient to drive the development of SS in lupus-prone mice.

Keywords

Acknowledgement

We thank the Analytical Instrumental Center (Seoul) at Hanyang University for technical support. This work was supported by grants funded by the Korean Health Technology R&D Project, Ministry of Health & Welfare, Korea (HI13C0016 and HI17C1103).

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