Interferon regulatory factor 8 (IRF8) (IRF8)

Interferon regulatory factor 8 (IRF8), also known as Interferon-induced protein 41 or ICSBP, is a member of the interferon regulatory factor (IRF) family of transcription factors. It is primarily expressed in hematopoietic cells, where it serves as a master regulator of myeloid and lymphoid lineage commitment, specifically essential for the development of monocytes, plasmacytoid dendritic cells, and B cells [UniProt, PubMed: 21844392]. IRF8 functions by forming heterodimers with other transcription factors, such as PU.1, to bind specific DNA sequences like the Ets-IRF composite elements (EICEs), thereby regulating the expression of genes involved in the immune response and cell cycle control [PubMed: 22343569]. In oncology, IRF8 is frequently silenced or downregulated in chronic myeloid leukemia (CML) and acute myeloid leukemia (AML), acting as a tumor suppressor whose loss promotes leukemogenesis [PubMed: 17438071]. Conversely, mutations in the IRF8 gene are associated with severe primary immunodeficiencies characterized by a lack of dendritic cells and increased susceptibility to mycobacterial infections [PubMed: 21572436]. Therapeutically, IRF8 is targeted indirectly by immunomodulatory drugs (IMiDs) like lenalidomide, which facilitate its proteasomal degradation in specific hematologic malignancies, and its expression can be induced by interferon therapies to restore normal cell differentiation [PubMed: 29101249, PubMed: 10748121].

Other names

Interferon consensus sequence-binding proteinICSBPICSBP1Interferon-induced protein 41IRF-8H-ICSBP

Transcriptional regulation of interferon-stimulated genes and targeted proteasomal degradation via the CRBN-CRL4 E3 ubiquitin ligase complex [PubMed: 29101249, UniProt]