IRF8

IRF8, or interferon regulatory factor 8, is a transcription factor of the IRF family. In mice it is known as Icsbp. The protein binds DNA at IRF elements and ISREs and regulates expression of genes involved in immune responses. IRF8 activity is modulated by signaling pathways triggered by interferons and microbial stimuli, and it can function as a monomer or as part of heterodimers with other IRFs.

IRF8 directs hematopoietic development: it promotes differentiation of monocytes and macrophages and restricts granulocytic development; it is essential for the development of plasmacytoid dendritic cells and conventional dendritic cells type 1 (cDC1). In B cell lineage, IRF8 supports early development and germinal center function; expression declines during plasma cell differentiation under Blimp-1 control.

IRF8 mechanisms involve interactions with other transcription factors, notably PU.1, and with other IRFs, forming networks that regulate lineage-specific gene expression. It also regulates genes involved in antigen presentation, cytokine signaling, and antimicrobial responses in innate immune pathways.

Aberrations in IRF8 expression or function have been associated with hematologic malignancies, including certain leukemias and lymphomas, reflecting its important role in cell fate decisions and immune regulation. IRF8 remains a focus of study for understanding immune cell development, the regulation of inflammatory responses, and the pathogenesis of related diseases.