Autoimmune Epithelitis and Chronic Inflammation in Sjögren’s Syndrome-Related Dry Eye Disease

Abstract

Autoimmune epithelitis and chronic inflammation are one of the characteristic features of the immune pathogenesis of Sjögren’s syndrome (SS)-related dry eye disease. Autoimmune epithelitis can cause the dysfunction of the excretion of tear fluid and mucin from the lacrimal glands and conjunctival epithelia and meibum from the meibomian glands. The lacrimal gland and conjunctival epithelia express major histocompatibility complex class II or human leukocyte antigen-DR and costimulatory molecules, acting as nonprofessional antigen-presenting cells for T cell and B cell activation in SS. Ocular surface epithelium dysfunction can lead to dry eye disease in SS. Considering the mechanisms underlying SS-related dry eye disease, this review highlights autoimmune epithelitis of the ocular surface, chronic inflammation, and several other molecules in the tear film, cornea, conjunctiva, lacrimal glands, and meibomian glands that represent potential targets in the treatment of SS-related dry eye disease.

AAV2/9-mediated gene transfer into murine lacrimal gland leads to a long-term targeted tear film modification

“… 29 Dry eye diseases (DEDs) account for the second leading cause of corneal defects, in which the loss of physiological tear film is the central pathophysiological element. 30 DEDs can arise from genetic diseases, such as Gougerot-Sjögren’s syndrome, 31 or from aging, with up to one-third of the elderly population being affected. 27 , 32 The third leading cause of corneal defects is NK, which is often associated with corneal microenvironment dysregulation.…”

View from the Biological Property: Insight into the Functional Diversity and Complexity of the Gut Mucus

“…Sjogren’s syndrome (SS) is a heterogeneous, multifactorial disease influenced by multiple factors such as genetic, environmental, and hormonal parameters, which include but are not limited to clinical and pathologic phenotypes from dry eye disease to chronic interstitial lung disease (ILD) to gut disease [ 175 ]. Despite the amount of research on SS, the underlying harm to various organs remains unknown [ 176 ]. Recently, some experimental evidence corroborated that not only does SS not only increases autophagy and death and diminishes goblet cell density but also reduces MEM formation via increased epithelial growth and adhesion molecule (ICAM)-1, human leukocyte antigen (HLA)-DR, and IL-6.…”

Molecular Mechanisms Linking Inflammation to Autoimmunity in Sjögren’s Syndrome: Identification of New Targets

“…The mechanism of apoptosis is implicated in a cascade of molecular events that lead to the development of autoimmune disorders [ 8 ]. In the last few decades, apoptosis has been hypothesized as a mechanism of cell death in the SGs of pSS patients on the basis of data collected using experimental SS mouse models [ 9 ], pointing to glandular epithelial cells as active players in this mechanism [ 10 ]. In fact, pSS patients present increased apoptosis in the salivary glandular epithelium and show the co-localization of Fas (Apo-1/CD95) antigen and Fas ligand (FasL) in ductal and acinar cells, suggesting that the trigger of the apoptotic cascade occurs through the Fas/FasL system [ 11 ].…”