Sjögren’s syndrome: An old tale with a new twist

Abstract

Sjögren's syndrome (SjS) is chronic autoimmune disease manifested by the loss of saliva and/or tear secretion by salivary and/or lacrimal glands, respectively. The pathogenesis of the disease remains elusive, perhaps due to the multiple triggers of the disease. However, substantial advances have been made in attempting to resolve the complexity of SjS using both animal models and human subjects. The primary objectives of this review are to provide a better understanding of the disease processes with major emphasis on the use of mouse models, how genetic predisposition plays a role in the natural history of the disease, as well as a presentation of new findings pertaining to the role of TH1, TH2, and TH17 cells in the pathogenesis of SjS.

Sexual dimorphic function of IL-17 in salivary gland dysfunction of the C57BL/6.NOD-Aec1Aec2 model of Sjögren’s syndrome

“…SjS is a chronic inflammatory disease which is in part mediated by perturbation of the glandular epithelial cells resulting in the homing of monocytes and neutrophils from blood or nearby draining lymph nodes2141. The infiltrating monocytes differentiate into macrophages and along with neutrophils, secrete inflammatory cytokines and chemokines to commence the influx of adaptive lymphocytes42.…”

“…The initial sequestration of inflammatory cells is thought to be mediated by some sort of glandular perturbation, e.g. abnormal gland development, aberrant patho-physiological changes, unregulated apoptosis, or atrophic gland function21. The recruitment of innate immune cells facilitates an influx of autoantigen-specific B and T cells.…”

Vasoactive intestinal peptide/vasoactive intestinal peptide receptor relative expression in salivary glands as one endogenous modulator of acinar cell apoptosis in a murine model of Sjögren's syndrome

“…This observation supports the hypothesis that acinar cells are involved actively in the pathogenesis of SS and provides new evidence to the search of early biomarkers for diagnosis and/or disease activity. At the prediabetic stage, the non-obese diabetic (NOD) mouse model of Sjögren's syndrome has the unique characteristic of developing a deep secretory dysfunction with mild infiltration of the glands [9][10][11] consistent with a structural-dysfunctional aetiology. In keeping with this, early neurotransmitter receptor-signalling alterations have been reported in NOD females' submandibular glands unrelated to the onset of the autoimmune response [12][13][14].…”

Mechanisms of Salivary Gland Secretory Dysfunction in Sjögren’s Syndrome

“…IFN R -/-) showed normal development of salivary glands, maintained secretory function, and failed to develop any SS-like phenotypes ). However, its parental strain NOD and a recently developed SS mouse model C57BL/6.NOD-Aec1Aec2 showed retarded salivary gland growth and acinar cell apoptosis prior to disease onset and proceed to developing full-blown disease phenotype including loss of secretory function (Lee, Tudares, and Nguyen 2009). This indicates that IFN-plays an important role in loss of secretory function in SS.…”