Primary Sjogren Syndrome: Focus on Innate Immune Cells and Inflammation

Chiara Rizzo, Giulia Grasso, Giulia Maria Destro Castaniti, Francesco Ciccia, Giuliana Guggino, Chiara Rizzo, Giulia Grasso, Giulia Maria Destro Castaniti, Francesco Ciccia, Giuliana Guggino

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.

Keywords: IFN signature; Sjogren syndrome; cytokines; inflammation; innate immunity; innate lymphoid cells.

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
The interplay between innate immune cells and the inflammation prone microenvironment in Primary Sjogren Syndrome (pSS). pSS is a multifactorial rheumatic disease: environmental stimuli, in genetic susceptible subjects, may trigger Salivary gland epithelial cells (SGECs) to express ligands, receptors and cytokines, such as IL-22, that act in a paracrine and autocrine way when determining the activation of several innate immune cells like NKs, ILC3s, DCs and macrophages. SGECs exhibit a subverted architecture mainly characterized by altered tight junctions. The pro-inflammatory milieu, boosted by a huge production of cytokines and chemokines, promotes the recruitment of more innate immune cells and finally drives the formation of GC-like structures, which are responsible for the in situ autoantibodies release. The aberrant production of VEGF determines chaotic neoangiogenesis; activated endothelial cells express ICAM-1 that mediates immune innate cells tissue infiltration. Mast cells contribute to fibrosis and fatty infiltration of salivary glands. MAIT cells display a dysfunctional activation with a consequent impaired production of protective cytokines. The overall immune response appears to be Th17 polarized, suggesting a pivotal role for this cytokine in pSS. APC: Antigen presenting cell; BAFF: B-cell activating factor; DC: Dendritic cell; GC: Germinal center; ICs: Immunecomplexes; ICAM-1: Intercellular adhesion molecule 1; IL-22R: IL-22 receptor; ILC3: Type 3 innate lymphoid cell; MAIT: Mucosa-associated invariant T cell; SGECs: Salivary gland epithelial cells; VEGF: Vascular endothelial growth factor.

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