Contributions of Major Cell Populations to Sjögren’s Syndrome

Abstract

Sjögren’s syndrome (SS) is a female dominated autoimmune disease characterized by lymphocytic infiltration into salivary and lacrimal glands and subsequent exocrine glandular dysfunction. SS also may exhibit a broad array of extraglandular manifestations including an elevated incidence of non-Hodgkin’s B cell lymphoma. The etiology of SS remains poorly understood, yet progress has been made in identifying progressive stages of disease using preclinical mouse models. The roles played by immune cell subtypes within these stages of disease are becoming increasingly well understood, though significant gaps in knowledge still remain. There is evidence for distinct involvement from both innate and adaptive immune cells, where cells of the innate immune system establish a proinflammatory environment characterized by a type I interferon (IFN) signature that facilitates propagation of the disease by further activating T and B cell subsets to generate autoantibodies and participate in glandular destruction. This review will discuss the evidence for participation in disease pathogenesis by various classes of immune cells and glandular epithelial cells based upon data from both preclinical mouse models and human patients. Further examination of the contributions of glandular and immune cell subtypes to SS will be necessary to identify additional therapeutic targets that may lead to better management of the disease.

Transcriptomic and Single-Cell Analysis Reveals Regulatory Networks and Cellular Heterogeneity in Mouse Primary Sjögren’s Syndrome Salivary Glands

“…Another revealing finding from these analyses is the expression of various genes in the epithelial cells that are typically associated with innate and acquired immune responses. This observation reaffirms the prevailing notion that the activated and inflamed state of the epithelial cells in pSS is likely to play a prominent role and be a major contributing factor to disease pathophysiology ( 33 – 36 ). Overall, our comprehensive studies have highlighted the importance of key signaling networks and pathways and offered new insights into the underlying molecular nature of the diverse and afflicted cellular subpopulations in pSS.…”

The Transcriptomic Profile of Monocytes from Patients With Sjögren’s Syndrome Is Associated With Inflammatory Parameters and Is Mimicked by Circulating Mediators

“…Primary Sjögren's syndrome (pSS) is a systemic autoimmune disease characterized by lymphocytic infiltration of the salivary and lachrymal glands leading to glandular destruction and dysfunction and B cell hyperactivity (1). Although pSS pathogenesis remains to be fully uncovered, the important contribution of monocytes is evident, not only in the initial immune response but also in the maintenance of chronic inflammation (2)(3)(4). Monocytes are highly specialized in phagocytosis and antigen presentation, secrete a large range of different cytokines and chemokines, and migrate to the tissues in response to infection and injury.…”

The Role of Interferons in the Pathogenesis of Sjögren’s Syndrome and Future Therapeutic Perspectives

“…Any cell is considered virtually able to produce type I IFNs [ 23 ], following stimulation by exogenous or endogenous nucleic acids. However, it has been shown that plasmacytoid dendritic cells (pDCs) are the main IFNα-producing cells.…”

“…In this target tissue, an overexpression of type II IFN signature has been reported to be present and associated with the development of lymphoma [ 47 ]. This different pattern is probably induced by the active participation in the local inflammatory process of other non-inflammatory cells, such as glandular epithelial cells [ 23 ]. The continuously increasing evidence of the differences of IFN expression in different subsets of patients with pSS supports the belief that any clinical phenotype may underlie a different pattern of immune and metabolic processes.…”