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The Role of Interferons in the Pathogenesis of Sjogren's Syndrome and Future Therapeutic Perspectives

BIOMOLECULES (2021)

Journal

BIOMOLECULES

Volume 11, Issue 2, Pages -

Publisher

MDPI

DOI: 10.3390/biom11020251

Keywords

type I interferon; type II interferon; Sjogren's syndrome; target therapies

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Abstract

Evidence suggests that interferons play a key role in the pathogenesis of systemic autoimmune diseases, such as primary Sjogren's syndrome. Overexpression of type I interferon is associated with systemic extra-glandular manifestations and production of autoantibodies, while a milder expression is linked to limited glandular involvement. The potential role of type II interferon and different immunological pathways in subset of pSS patients is an emerging area of study.

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 Sjogren'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 (IFN gamma) 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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Trained Immunity in Primary Sjogren's Syndrome: Linking Type I Interferons to a Pro-Atherogenic Phenotype

Erika Huijser, Cornelia G. van Helden-Meeuwsen, Dwin G. B. Grashof, Jessica R. Tarn, Zana Brkic, Josje M. A. Huisman, M. Javad Wahadat, Harmen J. G. van de Werken, Ana P. Lopes, Joel A. G. van Roon, Paul L. A. van Daele, Sylvia Kamphuis, Wan-Fai Ng, Siroon Bekkering, Leo A. B. Joosten, Willem A. Dik, Marjan A. Versnel

Summary: Trained immunity is a long-term reprogramming of innate immune cells that is linked to atherosclerosis. This study investigated the link between type I interferons and trained immunity in patients with primary Sjogren's syndrome. The findings suggest that type I interferon induces a trained immunity phenotype in monocytes, while trained immunity also affects the production of type I interferons.

FRONTIERS IN IMMUNOLOGY (2022)