TYK2 is essential for the therapeutic effect of IFN-α in <i>Jak2</i>V617F-induced murine myeloproliferative neoplasms.

ABSTRACT: Interferon-α (IFN-α) exhibits antiviral and antiproliferative effects on normal and neoplastic cells. Intracellular signaling of IFN-α is mediated by tyrosine kinase 2 (TYK2) and janus kinase 1 (JAK1), followed by signal transducers and activators of transcription (STATs). TYK2 is redundant for the antiviral effect of IFN-α; however, the requirements for antiproliferative effects are unknown. We assessed the role of TYK2 in the effects of IFN-α in myeloproliferative neoplasm (MPN) model mice. Jak2V617F transgenic mice develop MPNs resembling human primary myelofibrosis, and ropeginterferon-α-2b ameliorated their features. However, these IFN-α effects were absent in Jak2V617F;Tyk2 ^-/- mice. In mixed wild-type (WT)/Jak2V617F chimeric mice, IFN-α treatme

SUBMITTER: Tahira Y 

PROVIDER: S-EPMC12432513 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature