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Review
. 2024 Jul 17;29(1):371.
doi: 10.1186/s40001-024-01967-5.

Primary Sjögren's syndrome: new perspectives on salivary gland epithelial cells

Jiaqi Hou  1 , Yiyi Feng  1 , Zhixia Yang  1 , Yimei Ding  1 , Dandan Cheng  2 , Zhonghao Shi  1 , Rouxin Li  1 , Luan Xue  3
Affiliations
Review

Primary Sjögren's syndrome: new perspectives on salivary gland epithelial cells

Jiaqi Hou et al. Eur J Med Res. .

Abstract

Primary Sjögren's syndrome (pSS) is a chronic autoimmune disease primarily affecting exocrine glands such as the salivary glands, leading to impaired secretion and sicca symptoms. As the mainstay of salivation, salivary gland epithelial cells (SGECs) have an important role in the pathology of pSS. Emerging evidence suggests that the interplay between immunological factors and SGECs may not be the initial trigger or the sole mechanism responsible for xerostomia in pSS, challenging conventional perceptions. To deepen our understanding, current research regarding SGECs in pSS was reviewed. Among the extensive aberrations in cellular architecture and function, this review highlighted certain alterations of SGECs that were identified to occur independently of or in absence of lymphocytic infiltration. In particular, some of these alterations may serve as upstream factors of immuno-inflammatory responses. These findings underscore the significance of introspecting the pathogenesis of pSS and developing interventions _targeting SGECs in the early stages of the disease.

Keywords: Function; Pathogenesis; Primary Sjögren’s syndrome; Salivary gland epithelial cells; Structure.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Ultrastructural changes of SGECs in pSS. (1) Changes in apical membrane: altered localization of ezrin might lead to redistribution of AQP5 and F-actin, the latter of which might contribute to morphological aberration of microvilli. (2) Changes in lateral membrane: altered expression of occludin, claudin and ZO-1 disrupts the structure of TJs. TJ disruption can also lead to loss of microvillus architecture because they are connected via F-actin. (3) Changes in basal membrane: the expression of laminin and nidogen is altered, and MMPs are over-activated to degrade Type IV collagen and laminin. Meanwhile, the structure of hemidesmosomes is also deteriorated. Abbreviations: aquaporin, AQP; tight junction, TJ; matrix metalloproteinase, MMP
Fig. 2
Fig. 2
Aberrations in salivary secretory process. (1) Interfered neurotransmitter release; (2) M3R blockade/activation by antibody; (3) variants in M3R-related gene CHRM3; (4) inhibition of IP3R translation by the canonical function of miR-1248; (5) IP3R deficit; (6) reduction of RyR activity related to chronic NO elevation; (7) decreased expression of SERCA2b; (8) EBV-specific microRNA _targeting at STIM1; (9) altered ezrin localization and AQP5 trafficking; (10) altered activity of apical ion channels; (11) SNARE redistribution and abnormal exocytosis of mucins. Abbreviation: M3R, M3 muscarinic ACh receptor; NO, nitric oxide; IP3R, 1,4,5-triphosphate receptor; RyR, ryanodine receptor; EBV, Epstein–Barr virus; AQP5, aquaporin 5
Fig. 3
Fig. 3
Homeostasis disruption in SGECs. The homeostasis disruption in SGECs include apoptosis, endoplasmic stress, mitochondrial dysfunction, lysosome and autophagy dysfunction, and premature senescence of stem/progenitor cells. In the box, the dots represent manifestations, and the arrows represent consequences. UPR unfolded protein response, IRE inositol-requiring enzyme, ATF activating transcription factor, ERAD ER-associated protein degradation, GRP glucose-regulated protein, HEL hexanoyl-lysine, LMP lysosomal membrane permeabilization
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