Type I interferons in host defence and inflammatory diseases

Abstract

Type I interferons (IFN) can have dual and opposing roles in immunity, with effects that are beneficial or detrimental to the individual depending on whether IFN pathway activation is transient or sustained. Determinants of IFN production and its functional consequences include the nature of the microbial or nucleic acid stimulus, the type of nucleic acid sensor involved in inducing IFN, the predominant subtype of type I IFN produced and the immune ecology of the tissue at the time of IFN expression. When dysregulated, the type I IFN system drives many autoimmune and non-autoimmune inflammatory diseases, including SLE and the tissue inflammation associated with chronic infection. The type I IFN system may also contribute to outcomes for patients affected by solid cancers or myocardial infarction. Significantly more research is needed to discern the mechanisms of induction and response to type I IFNs across these diseases, and patient endophenotyping may help determine whether the cytokine is acting as ‘friend’ or ‘foe’, within a particular patient, and at the time of treatment. This review summarises key concepts and discussions from the second International Summit on Interferons in Inflammatory Diseases, during which expert clinicians and scientists evaluated the evidence for the role of type I IFNs in autoimmune and other inflammatory diseases.

Activation of plasmacytoid dendritic cells and B cells with two structurally different Toll‐like receptor 7 agonists

“…The pDCs are specialized to rapidly produce large amounts of type I IFN, especially IFN‐α, in response to a broad range of viruses and some bacteria 19,20 . Type I IFN also has powerful immunomodulatory effects that can be deleterious and increase the risk for autoimmune disease in genetically predisposed individuals 21‐24 . For example, in systemic lupus erythematosus (SLE) a continuous type I IFN production by pDCs is triggered by an endogenous stimulator consisting of nucleic acid containing immune complexes (IC), for example autoantibodies and nucleic acid binding proteins 24‐27 .…”

“…Type I IFN also has powerful immunomodulatory effects that can be deleterious and increase the risk for autoimmune disease in genetically predisposed individuals 21‐24 . For example, in systemic lupus erythematosus (SLE) a continuous type I IFN production by pDCs is triggered by an endogenous stimulator consisting of nucleic acid containing immune complexes (IC), for example autoantibodies and nucleic acid binding proteins 24‐27 . In addition, B cells can enhance the IFN‐α production by pDCs when stimulated by immune complexes consisting of small nuclear ribonucleoproteins and IgG isolated from SLE patients 4 .…”

Keeping up with the progress in the diagnosis and management of pediatric rheumatic diseases

“…Advances in high-throughput screening of small-molecule inhibitors accelerate the discovery of new and more specific therapeutic options. The recognition of the key role of interferons in the JDM and SLE is an important development [21]. Anifrolumab, a potential new treatment targeting interferon receptor, just successfully completed a phase three clinical trial called Treatment of Uncontrolled Lupus via the Interferon Pathway.…”

Protein tyrosine phosphatase non‐receptor type 22 (PTPN22) gene polymorphisms in liver transplant donors and impact on acute cellular liver transplant rejection

“…Furthermore, it has been reported that Lyp regulates type 1 interferon production after toll‐like receptor engagement in DCs . Type 1 interferon has pleiotropic effects, which include promoting the maturation of DCs into antigen‐presenting cells and B‐ and T‐cells survival, activation, and differentiation . In transplant setting type 1 interferon is involved in the induction of acute cellular graft rejection …”

“…10,11 Type 1 interferon has pleiotropic effects, which include promoting the maturation of DCs into antigen-presenting cells and B-and T-cells survival, activation, and differentiation. 12 In transplant setting type 1 interferon is involved in the induction of acute cellular graft rejection. 13,14 There are many SNPs in the gene of PTPN22.…”