The Role of Type III Interferons in Human Disease

Abstract

Purpose: This literature review summarizes the main immunological characteristics of type III interferons (IFN) and highlights the clinically relevant aspects and future therapeutic perspectives for these inflammatory molecules.
 
 Source: Relevant articles in PubMed MEDLINE from the first publication (2003) until 2020. N=101 articles were included in this review.
 
 Principal findings: Type III IFNs represent a relatively newly described inflammatory cytokine family. Although they induce substantially similar signalling to the well-known type I IFNs, significant functional differences make these molecules remarkable. Type III IFNs have extensive biological effects, contributing to the pathogenesis of several diseases and also offering new diagnostic and therapeutic approaches: 1) their potent anti-viral properties make them promising therapeutics against viral hepatitis and even against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is causing the current coronavirus disease 2019 (COVID-19) pandemic; 2) imbalances in the IFN-λs contribute to several forms of chronic inflammation (e.g., systemic and organ-specific autoimmune diseases) and potentially predict disease progression and therapeutic response to biologic therapies; and 3) the antitumor properties of the type III IFNs open up new therapeutic perspectives against malignant diseases.
 
 Conclusion: Over the last 18 years, researchers have gathered extensive information about the presence and role of these versatile inflammatory cytokines in human diseases, but further research is needed to clarify the mechanistic background of those observations. Better understanding of their biological activities will permit us to use type III IFNs more efficiently in new diagnostic approaches and individualized therapies, consequently improving patient care.

The Immunotherapeutic Role of Type I and III Interferons in Melanoma and Non-Melanoma Skin Cancers

“…Type III IFNs consist of four subtypes of IFN-λ: IFN-λ1 (IL-29), IFN-λ2 (IL-28A), IFN-λ3 (IL-28B), and IFN-λ4 [ 17 ]. They signal through heterodimeric receptors with one chain of IFN-λ receptor 1 (IFNLR1) and one chain of interleukin-10 receptor 2 (IL-10R2) [ 18 , 19 , 20 ].…”

“…They signal through heterodimeric receptors with one chain of IFN-λ receptor 1 (IFNLR1) and one chain of interleukin-10 receptor 2 (IL-10R2) [ 18 , 19 , 20 ]. The IL-10-R2 chain is ubiquitously expressed, while the IFNLR1 receptor is only expressed in cells of epithelial origin, plasmacytoid dendritic cells, neutrophils, NK cells, and B cells [ 17 ]. Structurally, type III IFNs are related to type I IFNs and the IL-10 family.…”

“…The key difference between the two is that type III IFN has a smaller spectrum of ISG activation. Furthermore, type III IFNs do not induce any unique ISGs, and compared with type I IFNs, type IIIs have a lower magnitude but longer-lasting ISG induction [ 17 ]. Despite the substantial overlap in their signaling cascade, growing evidence suggests spatial and kinetic differences in type I and type III IFN responses, thus leading to unique context-specific functional responses, reviewed in detail elsewhere [ 2 ].…”

Clinical efficacy of selenium supplementation in patients with Hashimoto thyroiditis: A systematic review and meta-analysis

“…Selenoproteins are involved in thyroid hormone metabolism and regulation of the redox state and reduce the inflammatory status in patients with HT. [12,26] Selenium deficiency contributes to decreased activity of glutathione peroxidases and deiodinases, which can lead to oxidative damage and the synthesis of triiodothyronine. [7,27] Due to the high degree of heterogeneity between studies, we conducted meta-regression and subgroup analyses based on sample size, percentage of females, mean age, baseline antibody (TPOAb and TgAb) levels, and baseline thyrotropin levels.…”

“…Selenoproteins are involved in thyroid hormone metabolism and regulation of the redox state and reduce the inflammatory status in patients with HT. [ 12 , 26 ] Selenium deficiency contributes to decreased activity of glutathione peroxidases and deiodinases, which can lead to oxidative damage and the synthesis of triiodothyronine. [ 7 , 27 ]…”