Interferon regulatory factor 8 (IRF8)

Interferon regulatory factor 8 (IRF8) is a nuclear transcription factor highly expressed in hematopoietic cells, particularly myeloid lineage cells, where it orchestrates immune cell differentiation, cytokine production, autophagy, and apoptosis[3][5][1]. IRF8 forms multi-protein complexes with other transcription factors (e.g., IRF4, BATF, PU.1, ETV6), allowing it to function as either a transcriptional activator or repressor depending on its binding partners[5][2]. It regulates genes involved in immune responses to pathogens, the control of myeloid-derived suppressor cell (MDSC) development, and tumor suppression through modulation of cell death pathways and prevention of immune evasion. IRF8 silencing, especially via promoter methylation in cancer, is a mechanism of disease progression and therapeutic resistance. IRF8 expression levels are clinically relevant as biomarkers for immunotherapy selection and monitoring, and it is implicated as a therapeutic target in cancer, autoimmunity, and infectious disease contexts[5][1][2][3].

Other names

ICSBPICSBP1IRF-8H-ICSBPInterferon consensus sequence-binding proteinInterferon consensus sequence binding protein 1

Modulation of gene expression affecting immune and survival pathways. Regulation of target antigen expression (e.g., CD20 for rituximab/ ofatumumab efficacy). Sensitization to apoptosis (e.g., via Fas-mediated pathways). Regulation of cytokine response.