Type 1 interferons: A target for immune-mediated inflammatory diseases (IMIDs)

The improved understanding of the molecular basis of innate immunity have led to the identification of type I interferons (IFNs), particularly IFN-a, as central mediators in the pathogenesis of several Immunemediated inflammatory diseases (IMIDs) such as systemic lupus erythematosus (SLE), systemic sclerosis, inflammatory myositis and Sjogren's syndrome. Here, we review the main data regarding the opportunity to target type I IFNs for the treatment of IMIDs. Type I IFNs and their downstream pathways can be targeted pharmacologically in several manners. One approach is to use monoclonal antibodies against IFNs or the IFN-receptors (IFNARs, such as with anifrolumab). The downstream signaling pathways of type I IFNs also contain several targets of interest in IMIDs, such as JAK1 and Tyk2. Of these, anifrolumab is licensed and JAK1/Tyk2 inhibitors are in phase III trials in SLE. Targeting IFN-Is for the treatment of SLE is already a reality and in the near future may prove useful in other IMIDs. IFN assays will find a role in routine clinical practice for the care of IMIDs as further validation work is completed and a greater range of targeted therapies becomes available. (c) 2023 Societe franc, aise de rhumatologie. Published by Elsevier Masson SAS. All rights reserved.

Automated summary

Improved understanding of the molecular basis of innate immunity has led to the recognition of type I interferons (IFNs) as key mediators in the development of immunemediated inflammatory diseases (IMIDs). Pharmacological targeting of IFNs and their downstream signaling pathways, such as JAK1 and Tyk2, holds promise for the treatment of IMIDs.