Role of the Innate Immunity Signaling Pathway in the Pathogenesis of Sjögren’s Syndrome

Sjögren’s syndrome (SS) is a systemic autoimmune disease characterized by chronic inflammation of the salivary and lacrimal glands and extra-glandular lesions. Adaptive immune response including T- and B-cell activation contributes to the development of SS. However, its pathogenesis has not yet been elucidated. In addition, several patients with SS present with the type I interferon (IFN) signature, which is the upregulation of the IFN-stimulated genes induced by type I IFN. Thus, innate immune responses including type I IFN activity are associated with SS pathogenesis. Recent studies have revealed the presence of activation pattern recognition receptors (PRRs) including Toll-like receptors, RNA sensor retinoic acid-inducible gene I and melanoma differentiation-associated gene 5, and inflammasomes in infiltrating and epithelial cells of the salivary glands among patients with SS. In addition, the activation of PRRs via the downstream pathway such as the type I IFN signature and nuclear factor kappa B can directly cause organ inflammation, and it is correlated with the activation of adaptive immune responses. Therefore, this study assessed the role of the innate immune signal pathway in the development of inflammation and immune abnormalities in SS.

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

Biomolecules ◽

10.3390/biom11020251 ◽

2021 ◽

Vol 11 (2) ◽

pp. 251

Author(s):

Nicoletta Del Papa ◽

Antonina Minniti ◽

Maurizio Lorini ◽

Vincenzo Carbonelli ◽

Wanda Maglione ◽

...

Keyword(s):

Sjögren’S Syndrome ◽

Inflammatory Cytokines ◽

Sjögren's Syndrome ◽

Sjogren’S Syndrome ◽

Sjogren's Syndrome ◽

Type I ◽

Type Ii ◽

Type I Ifn ◽

Sjögren‘S Syndrome

There is a great deal of evidence pointing to interferons (IFNs) as being key cytokines in the pathogenesis of different systemic autoimmune diseases, including primary Sjögren’s syndrome (pSS). In this disease, a large number of studies have shown that an overexpression of type I IFN, the ‘so-called’ type I IFN signature, is present in peripheral blood mononuclear cells, and that this finding is associated with the development of systemic extra-glandular manifestations, and a substantial production of autoantibodies and inflammatory cytokines. In contrast, the absence or a milder expression of type I IFN signature and low level of inflammatory cytokines characterizes patients with a different clinical phenotype, where the disease is limited to glandular involvement and often marked by the presence of widespread pain and depression. The role of type II (IFNγ) in this subset of pSS patients, together with the potentially related activation of completely different immunological and metabolic pathways, are emerging issues. Expression of both types of IFNs has also been shown in target tissues, namely in minor salivary glands where a predominance of type II IFN signature appeared to have a certain association with the development of lymphoma. In view of the role played by IFN overexpression in the development and progression of pSS, inhibition or modulation of IFN signaling has been regarded as a potential target for the therapeutic approach. A number of therapeutic compounds with variable mechanisms of action have been tested or are under consideration for the treatment of patients with pSS.

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