Interferon regulatory factors (IRFs) comprise a family of transcription factors that function within the Jak/Stat pathway to regulate interferon (IFN) and IFN-inducible gene expression in response to viral infection (1). IRFs play an important role in pathogen defense, autoimmunity, lymphocyte development, cell growth and susceptibility to transformation. The IRF family includes nine members: IRF-1, IRF-2, ISGF3g/p48, IRF-3, IRF-4 (Pip/LSIRF/ICSAT), IRF-5, IRF-6, IRF-7 and IRF-8/ICSBP. All IRF proteins share homology in their amino-terminal DNA binding domains. IRF family members regulate transcription through interactions with proteins that share similar DNA binding motifs, such as IFN-stimulated response elements (ISRE), IFN consensus sequences (ICS) and IFN regulatory elements (IRF-E) (2). IRF-8/ICSCP is expressed predominately in hematopoietic cells and is further increased upon treatment with interferon (3,4). IRF-8 can function as a transcription repressor of ICS-containing promoters (4). Expression of IRF-8 can lead to the down-regulation of the anti-apoptotic protein Bcl-2 (5). Originally described as being induced by IFN-y, IRF-8 expression is also elevated by IRF-a as well as IL-12 in NK and T cells (6). IRF-8 deficient mice have enhanced susceptibility to various pathogens and impaired production of interferons, as well as deregulated hematopoiesis that resembles chronic myelogenous leukemia (7,8). IRF-8 also regulates bone metabolism by suppressing osteoclast formation (9).