Immune Netw.  2019 Dec;19(6):e44. 10.4110/in.2019.19.e44.

Autoantibody-Mediated Dysfunction of Salivary Glands Leads to Xerostomia in SKG Mice

Affiliations
  • 1Laboratory of Autoimmunology, Department of Anatomy and Cell Biology, Hanyang University College of Medicine, Seoul 04763, Korea. jhyoun@hanyang.ac.kr
  • 2Department of Pathology, Hanyang University College of Medicine, Seoul 04763, Korea.
  • 3Department of Physiology, Hanyang University College of Medicine, Seoul 04763, Korea.
  • 4Division of Oral & Maxillofacial Surgery, Department of Dentistry, Hanyang University College of Medicine, Seoul 04763, Korea.

Abstract

Sjögren's syndrome (SS) is a chronic heterogeneous disease that mainly affects exocrine glands, leading to sicca syndromes such as xerostomia. Despite the second highest prevalence rate among systemic autoimmune diseases, its pathophysiology remains largely unknown. Here we report that SKG mice, a cardinal model of Th17 cell-mediated arthritis, also develop a secondary form of SS-like disorder upon systemic exposure to purified curdlan, a type of β-glucan. The reduced production of saliva was not caused by focal immune cell infiltrates but was associated with IgG deposits in salivary glands. Sera from curdlan-injected SKG mice contained elevated titers of IgG (predominantly IgG1), autoantibody to the muscarinic type 3 receptor (M3R) and inhibited carbachol-induced Ca2+ signaling in salivary acinar cells. These results suggest that the Th17 cells that are elicited in SKG mice promote the production of salivary gland-specific autoantibodies including anti-M3R IgG; the antibodies are then deposited on acinar cells and inhibit M3R-mediated signaling required for salivation, finally leading to hypofunction of the salivary glands. This type II hypersensitivity reaction may explain the origin of secondary SS occurring without focal leukocyte infiltrates.

Keyword

Sjogren's Syndrome; Xerostomia; Autoantibodies

MeSH Terms

Acinar Cells
Animals
Antibodies
Arthritis
Autoantibodies
Autoimmune Diseases
Exocrine Glands
Hypersensitivity
Immunoglobulin G
Leukocytes
Mice*
Prevalence
Saliva
Salivary Glands*
Salivation
Sjogren's Syndrome
Th17 Cells
Xerostomia*
Antibodies
Autoantibodies
Immunoglobulin G
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