IRF4

IRF4, or Interferon Regulatory Factor 4, also known as MUM1, is a member of the interferon regulatory factor transcription factor family. The IRF4 protein contains a DNA-binding domain that recognizes interferon-stimulated response elements and modulates transcription of genes involved in immune responses.

In the immune system, IRF4 is expressed in B cells, T cells, plasmacytoid dendritic cells, and macrophages, and is upregulated upon activation by antigen receptor signaling, CD40 ligation, Toll-like receptor signaling, and cytokines.

In B cells, IRF4 regulates development and differentiation, participating in germinal center formation, promoting class-switch recombination, and driving plasma cell differentiation by inducing PRDM1 (BLIMP-1) and XBP1. IRF4 works with PU.1 to regulate lineage-specific genes and helps coordinate the antibody response.

In T cells, IRF4 influences differentiation, notably promoting Th2 and Th17 programs, and contributes to the function of other helper and regulatory T cell subsets in conjunction with signaling pathways.

Clinical significance: IRF4 overexpression or translocations involving IGH-IRF4 are characteristic of certain B-cell malignancies, particularly multiple myeloma and plasmacytomas. IRF4 was historically named MUM1 and remains a diagnostic immunohistochemical marker for plasmacytoid differentiation.

Genetics and translocations: In multiple myeloma, a subset carries the t(6;14)(p25;q32) translocation placing IRF4 under control of the IGH locus, leading to IRF4 overexpression and contributing to disease biology.

IRF4 remains a central regulator of adaptive immunity and a focus of research into vaccines and cancer therapy due to its pivotal role in lymphocyte differentiation and function.