Among the family of interferons (IFNs), type III IFNs (or IFN-?s) were the most recently discovered. Four members of this family are known in humans (IFN-?1,2,3 and IFN-?4) but only IFN-?2,3 are expressed in mice. Since their discovery, it has been evident that they share many characteristics with type I IFNs. Indeed, they induce overlapping transcriptional signatures that include many Interferon Stimulated Genes with antiviral functions. However, over the years, IFN-?s have emerged as a highly specialized group of cytokines uniquely suited to mediate antiviral protection at mucosal barriers. This specialization of IFN-?s stems not only from the pattern of expression of their specific receptor, which is mostly restricted to cells of epithelial lineage and a selected pool of immune cells but also from their unique immunomodulatory properties that limit damaging responses while favoring protective immunity.
The role of IFN-?s in the control of viral infections of the mucosae has been extensively studied, however, recent advances in the study of IFN-? biology paint a more complex picture. Indeed, non-redundant activities of IFN-?s compared to type I IFNs during viral restriction are emerging and still the object of intense investigation. Recently, IFN-?s were shown to have the capacity to influence the immune response in a variety of non-viral infectious pathologies and they have been shown to be produced in response and to protect against different classes of microbes, including bacteria and fungi. Several studies indicate that IFN-?s can have broader immunomodulatory functions with important consequences on the regulation of the innate and adaptive immune response. Indeed, IFN-?s were shown to be important during non-infectious immune pathologies in the lung and the intestine. The aim of this Research Topic is therefore to highlight the emerging and intriguing properties of IFN-?s, to understand the unique mechanisms that control their site-specific functions, and to give perspective on how the field of IFN-?s is evolving beyond mucosal antiviral immunity.
We welcome the submission of Reviews and Original Research articles. We specifically encourage the submission of Mini Reviews and Perspectives, covering new and understudied roles of IFN-?s with particular emphasis on how these features can evolve as contributions to the field of IFN-? biology. We also encourage the submission of Original Research papers covering provocative and novel IFN-? functions. Examples of themes that will be covered in this Research Topic are:
1. Nonredundant roles of IFN-? in the protection against viruses
2. Basal levels of IFN-? at mucosal surfaces and their relationship with the microbiome
3. IFN-? beyond antiviral immunity: Protection against non-viral pathogens at mucosal sites
4. IFN-? and immune cells: innate and adaptive immunomodulatory roles of Type III IFNs
5. The enigmatic role of IFN-?4 in humans: patterns of expression and mechanisms of action
6. IFN-? distribution and functions
7. IFN-? as a therapeutic cytokine
8. Regulation of IFN-? signaling: epigenetics and signal transduction regulation of IFN-? responses
