Mouse Models of Primary Sjogren’s Syndrome

Abstract

Sjögren’s syndrome (SjS) is a chronic autoimmune disorder characterized by immune cell infiltration and progressive injury to the salivary and lacrimal glands. As a consequence, patients with SjS develop xerostomia (dry mouth) and keratoconjunctivitis sicca (dry eyes). SjS is the third most common rheumatic autoimmune disorder, affecting 4 million Americans with over 90% of patients being female. Current diagnostic criteria for SjS frequently utilize histological examinations of minor salivary glands for immune cell foci, serology for autoantibodies, and dry eye evaluation by corneal or conjunctival staining. SjS can be classified as primary or secondary SjS, depending on whether it occurs alone or in association with other systemic rheumatic conditions, respectively. Clinical manifestations typically become apparent when the disease is relatively advanced in SjS patients, which poses a challenge for early diagnosis and treatment of SjS. Therefore, SjS mouse models, because of their close resemblance to the human SjS, have been extremely valuable to identify early disease markers and to investigate underlying biological and immunological dysregulations. However, it is important to bear in mind that no single mouse model has duplicated all aspects of SjS pathogenesis and clinical features, mainly due to the multifactorial etiology of SjS that includes numerous susceptibility genes and environmental factors. As such, various mouse models have been developed in the field to try to recapitulate SjS. In this review, we focus on recent mouse models of primary SjS and describe them under three categories of spontaneous, genetically engineered, and experimentally induced development of SjS-like disease. In addition, we discuss future perspectives of SjS mouse models highlighting pros and cons of utilizing mouse models and demands for improved models.

Enriching Islet Phospholipids With Eicosapentaenoic Acid Reduces Prostaglandin E2 Signaling and Enhances Diabetic β-Cell Function

“…We used both male ( N = 11) and female mice ( N = 13), and subjected them to control or EPA-enriched diet feeding from weaning (3 to 4 weeks of age) until 17 weeks of age, a time period during which NOD mice have been reported to develop β-cell failure and overt hyperglycemia (23). Only one female mouse developed hyperglycemia during this timeframe, though (from the EPA-enriched diet group); therefore, we restricted our analysis to the nondiabetic mice.…”

What can Sjögren's syndrome-like disease in mice contribute to human Sjögren's syndrome?

“…As a result, to study the pathophysiological and immunological nature of this autoimmune disease, numerous mouse models have been developed that presumably mimic specific characteristics common to the human disease. The potential relevance of these mouse lines, along with the genetic bases for their disease phenotypes, are discussed in detail in several recent reviews [15,16]. Nevertheless, there remain serious concerns that these SS-like models are often artificial, exhibit at best only partial disease, and do not sufficiently represent the clinical human disease.…”

Lacrimal gland development: From signaling interactions to regenerative medicine

“…The most significant risk factor for dry eye disease is aging, associated with structural and functional changes in the lacrimal gland characterized by atrophied acini, duct obstruction, lymphocytic infiltration and decreased protein secretion (Rocha et al, 2008). Lacrimal gland dysfunction can also arise from inflammation triggered by the dry environment, auto-immune attack as in Sjogren’s syndrome and rheumatoid arthritis, side effects of chemo and radiation therapies, as well as congenital defects (Javadi and Feizi, 2011; He et al, 2013; Park et al, 2015). Several treatments exist, including punctal occlusion to reduce tear drainage, anti-inflammatory drugs such as topical cyclosporine and lifitegrast, and most commonly artificial tears and gels (Babic et al, 2010).…”