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Salivary gland progenitor cells and epithelium in primary Sjögren’s syndrome

Pathology and treatment
PhD ceremony:X. (Xiaoyan) Wang
When:October 28, 2020
Supervisors:prof. dr. F.G.M. (Frans) Kroese, prof. dr. H. (Hendrika) Bootsma
Co-supervisor:dr. S.A. (Sarah) Pringle
Where:Academy building RUG
Faculty:Medical Sciences / UMCG
Salivary gland progenitor cells and epithelium in primary
Sjögren’s syndrome

Primary Sjögren’s syndrome (pSS) is a proinflammatory systemic autoimmune disease, characterized by dysfunction of exocrine glands (salivary and lacrimal glands) with glandular lymphocytic infiltration and autoantibody production, amongst many other systemic symptoms. The salivary gland (SG) is a primary target of pSS. Dysfunction of SG in pSS not only leads to oral dryness but is often accompanied by other oral difficulties, for example, dental caries, recurrent mouth infections, and problems with eating and speaking. However, the etiology of dry mouth development in pSS remains unresolved. Many current interventions in pSS focus on alleviating patient symptoms, for instance, using pilocarpine to stimulate saliva production. In pSS patient SGs, epithelial cells play a central role in the development of SG dysfunction, not only as primary targets of an inflamed, autoimmune environment, but also by their ability to perform a variety of immunological functions. Salivary gland progenitor cells (SGPCs) are epithelial cells that maintain the homeostasis of SG by self-replication, and differentiation into saliva producing acinar cells. The aims of the studies in this thesis can be described in the following three points: (1) to study whether dysregulated epithelial cells and SGPCs are involved in pSS, (2) to investigate the senescence state of epithelial progenitor cells in pSS and other autoimmune diseases and the possible influence of this senescence on pSS, and (3) to explore the possible pathways that could modulate the proliferation and differentiation abilities of SGPCs, which could be hopefully used for future treatment strategies of pSS.