4.5 Review

Heterogeneity and functions of the 13 IFN-a subtypes - lucky for some?

Journal

EUROPEAN JOURNAL OF IMMUNOLOGY
Volume -, Issue -, Pages -

Publisher

WILEY
DOI: 10.1002/eji.202250307

Keywords

Autoantibodies; Autoimmunity; IFN-a,& nbsp;Infection; Type I IFNs

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This review summarizes the evidence on the differential functions of IFN-a subtypes and highlights potential reasons for discrepancies between reports. Both acute and chronic viral infections, as well as autoimmunity, are examined, with a focus on the role of anti-IFN-a autoantibodies in shaping the type I IFN responses in these different conditions.
Type I IFNs are critical for host responses to viral infection and are also implicated in the pathogenesis of multiple autoimmune diseases. Multiple subtypes exist within the type I IFN family, in particular 13 distinct IFN-a genes, which signal through the same heterodimer receptor that is ubiquitously expressed by mammalian cells. Both evolutionary genetic studies and functional antiviral assays strongly suggest differential functions and activity between the 13 IFN-a subtypes, yet we still lack a clear understanding of these different roles. This review summarizes the evidence from studies describing differential functions of IFN-a subtypes and highlights potential reasons for discrepancies between the reports. We examine both acute and chronic viral infection, as well as autoimmunity, and integrate a more recent awareness of the importance of anti-IFN-a autoantibodies in shaping the type I IFN responses in these different conditions.

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