Primary Sjogren Syndrome: Focus on Innate Immune Cells and Inflammation

Abstract

Primary Sjogren Syndrome (pSS) is a complex, multifactorial rheumatic disease that mainly targets salivary and lacrimal glands, inducing epithelitis. The cause behind the autoimmunity outbreak in pSS is still elusive; however, it seems related to an aberrant reaction to exogenous triggers such as viruses, combined with individual genetic pre-disposition. For a long time, autoantibodies were considered as the hallmarks of this disease; however, more recently the complex interplay between innate and adaptive immunity as well as the consequent inflammatory process have emerged as the main mechanisms of pSS pathogenesis. The present review will focus on innate cells and on the principal mechanisms of inflammation connected. In the first part, an overview of innate cells involved in pSS pathogenesis is provided, stressing in particular the role of Innate Lymphoid Cells (ILCs). Subsequently we have highlighted the main inflammatory pathways, including intra- and extra-cellular players. A better knowledge of such processes could determine the detection of new therapeutic targets that are a major need for pSS.

Autophagy, apoptosis, necroptosis, pyroptosis and netosis in pathogenesis of immune-inflammatory rheumatic diseases

“…Воспаление при ИВРЗ является преимущественно продуктивным, сопровождающимся появлением эндогенных сигналов опасности, называемых «ассоциированные с повреждением молекулярные паттерны», или DAMP. Отличительной особенностью DAMP является их способность взаимодействовать с рецепторами врожденного иммунитета (TLR2, TLR4, TLR7, TLR9), экспрессирующихся на фолликулярных и плазмацитоидных дендритных клетках (пДК и фДК) и активировать их [155].…”

The Involvement of Innate and Adaptive Immunity in the Initiation and Perpetuation of Sjögren’s Syndrome

“…Macrophages are activated by interferon gamma (IFN-γ) and interleukin (IL)-17 secreted by type 1 T helper cells (Th1) and type 17 T helper cells (Th17), respectively [ 23 ]. Activated macrophages produce inflammatory cytokines such as IL-1, tumor necrosis factor alpha (TNFα), IL-18, and metalloproteases (MMPs) leading to epithelial cell damage [ 24 , 25 ]. Activated macrophages can also act as antigenic peptide presenting cells through their major histocompatibility complex class II (MHC-II) and interact with antigen-specific CD4+ T cells [ 23 ].…”

“…Activated macrophages can also act as antigenic peptide presenting cells through their major histocompatibility complex class II (MHC-II) and interact with antigen-specific CD4+ T cells [ 23 ]. The latter, once activated, evolves in autoreactive clones that may perpetuate the activation of macrophages, themselves sustaining a pro-inflammatory auto-maintained loop [ 25 ].…”

Management of Sjögren's Syndrome: Present Issues and Future Perspectives

“…All of these cell types variably contribute to the formation of inflammatory infiltrates that, in some cases, may assume the aspect of tertiary ectopic germinal-like centers (teGLCs) ( 20 ). The attracted macrophages produce large amounts of inflammatory cytokines, namely IL-1 and TNFα, which lead to local tissue damage ( 21 , 22 ). In addition, in activated SGECs the apoptotic mechanism is triggered ( 23 ), with the subsequent release of autoantigens into the environment via autoantigen-containing apoptotic blebs and exosomes ( 24 , 25 ).…”