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Gene Review

Irf8  -  interferon regulatory factor 8

Mus musculus

Synonyms: AI893568, ICSBP, IRF-8, Icsbp, Icsbp1, ...
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Disease relevance of Irf8


High impact information on Irf8

  • ICSBP retrovirus-transduced cells differentiated into mature macrophages with phagocytic activity, which coincided with the induction of specific target DNA binding activity [6].
  • Together, ICSBP has a key role in the myeloid cell lineage selection and macrophage maturation [6].
  • ICSBP directs bipotential myeloid progenitor cells to differentiate into mature macrophages [6].
  • Contrary to this, ICSBP transducion led to repression of granulocyte-specific genes and inhibited G-CSF-mediated granulocytic differentiation in these and other myeloid progenitor cells [6].
  • Remarkably, the evolution of Alox15 MPD to leukemia is associated with additional regulation of ICSBP on an RNA level, highlighting the potential usefulness of the Alox15 model for understanding the transition of CML to crisis [7].

Biological context of Irf8


Anatomical context of Irf8

  • Immature ICSBP(-/-) DCs developed from BM progenitor cells showed assorted defects, did not mature in response to activation signals, and failed to express CD8alpha and interleukin 12 (IL-12) p40, a feature consistent with ICSBP(-/-) DCs in vivo [3].
  • We have found that although ISG15 expression is unchanged in B cells, it is upregulated in macrophages from ICSBP-/- mice [9].
  • However, transduction of retrovirus-ICSBP in the absence of IFN-gamma activation did not induce iNOS expression in either RAW264.7 cells or ICSBP-/- macrophages [10].
  • Once T cells were activated, ICSBP was expressed stably in both Th1 and Th2 cells [11].
  • Unlike other members of the family, ICSBP is expressed exclusively in the immune system [11].

Associations of Irf8 with chemical compounds


Physical interactions of Irf8


Regulatory relationships of Irf8

  • In this paper, we investigated whether ICSBP modulates the growth-promoting activity of Bcr/Abl, the causal oncoprotein for CML [18].
  • AML1-ETO inhibits maturation of multiple lymphohematopoietic lineages and induces myeloblast transformation in synergy with ICSBP deficiency [19].
  • Studies of proapoptotic genes showed that cells overexpressing ICSBP have enhanced expression of caspase-3 precursor protein [20].
  • Interferon (IFN) consensus sequence-binding protein (ICSBP) is an important transcription factor regulating proinflammatory cytokine production and the development of mononuclear phagocytes in vitro [21].

Other interactions of Irf8


Analytical, diagnostic and therapeutic context of Irf8


  1. A mutation in the Icsbp1 gene causes susceptibility to infection and a chronic myeloid leukemia-like syndrome in BXH-2 mice. Turcotte, K., Gauthier, S., Tuite, A., Mullick, A., Malo, D., Gros, P. J. Exp. Med. (2005) [Pubmed]
  2. Crucial role of interferon consensus sequence binding protein, but neither of interferon regulatory factor 1 nor of nitric oxide synthesis for protection against murine listeriosis. Fehr, T., Schoedon, G., Odermatt, B., Holtschke, T., Schneemann, M., Bachmann, M.F., Mak, T.W., Horak, I., Zinkernagel, R.M. J. Exp. Med. (1997) [Pubmed]
  3. ICSBP/IRF-8 retrovirus transduction rescues dendritic cell development in vitro. Tsujimura, H., Tamura, T., Gongora, C., Aliberti, J., Reis e Sousa, C., Sher, A., Ozato, K. Blood (2003) [Pubmed]
  4. Interferon-gamma induces regression of epithelial cell carcinoma: critical roles of IRF-1 and ICSBP transcription factors. Egwuagu, C.E., Li, W., Yu, C.R., Che Mei Lin, M., Chan, C.C., Nakamura, T., Chepelinsky, A.B. Oncogene (2006) [Pubmed]
  5. Accumulation of c-Cbl and rapid termination of colony-stimulating factor 1 receptor signaling in interferon consensus sequence binding protein-deficient bone marrow-derived macrophages. Kallies, A., Rosenbauer, F., Scheller, M., Knobeloch, K.P., Horak, I. Blood (2002) [Pubmed]
  6. ICSBP directs bipotential myeloid progenitor cells to differentiate into mature macrophages. Tamura, T., Nagamura-Inoue, T., Shmeltzer, Z., Kuwata, T., Ozato, K. Immunity (2000) [Pubmed]
  7. Identification of 12/15-lipoxygenase as a suppressor of myeloproliferative disease. Middleton, M.K., Zukas, A.M., Rubinstein, T., Jacob, M., Zhu, P., Zhao, L., Blair, I., Pur??, E. J. Exp. Med. (2006) [Pubmed]
  8. Interferon consensus sequence binding protein-deficient mice display impaired resistance to intracellular infection due to a primary defect in interleukin 12 p40 induction. Scharton-Kersten, T., Contursi, C., Masumi, A., Sher, A., Ozato, K. J. Exp. Med. (1997) [Pubmed]
  9. Interferon consensus sequence binding protein and interferon regulatory factor-4/Pip form a complex that represses the expression of the interferon-stimulated gene-15 in macrophages. Rosenbauer, F., Waring, J.F., Foerster, J., Wietstruk, M., Philipp, D., Horak, I. Blood (1999) [Pubmed]
  10. Complex formation of the interferon (IFN) consensus sequence-binding protein with IRF-1 is essential for murine macrophage IFN-gamma-induced iNOS gene expression. Xiong, H., Zhu, C., Li, H., Chen, F., Mayer, L., Ozato, K., Unkeless, J.C., Plevy, S.E. J. Biol. Chem. (2003) [Pubmed]
  11. Expression of IFN regulatory factor family proteins in lymphocytes. Induction of Stat-1 and IFN consensus sequence binding protein expression by T cell activation. Nelson, N., Kanno, Y., Hong, C., Contursi, C., Fujita, T., Fowlkes, B.J., O'Connell, E., Hu-Li, J., Paul, W.E., Jankovic, D., Sher, A.F., Coligan, J.E., Thornton, A., Appella, E., Yang, Y., Ozato, K. J. Immunol. (1996) [Pubmed]
  12. Interferon regulatory factor 8 regulates RANTES gene transcription in cooperation with interferon regulatory factor-1, NF-kappaB, and PU.1. Liu, J., Ma, X. J. Biol. Chem. (2006) [Pubmed]
  13. Identification of target genes and a unique cis element regulated by IRF-8 in developing macrophages. Tamura, T., Thotakura, P., Tanaka, T.S., Ko, M.S., Ozato, K. Blood (2005) [Pubmed]
  14. Modulation of interferon consensus sequence binding protein mRNA in murine peritoneal macrophages. Induction by IFN-gamma and down-regulation by IFN-alpha, dexamethasone, and protein kinase inhibitors. Politis, A.D., Sivo, J., Driggers, P.H., Ozato, K., Vogel, S.N. J. Immunol. (1992) [Pubmed]
  15. Toward the identification of a tolerogenic signature in IDO-competent dendritic cells. Orabona, C., Puccetti, P., Vacca, C., Bicciato, S., Luchini, A., Fallarino, F., Bianchi, R., Velardi, E., Perruccio, K., Velardi, A., Bronte, V., Fioretti, M.C., Grohmann, U. Blood (2006) [Pubmed]
  16. IFN-gamma up-regulates IL-18 gene expression via IFN consensus sequence-binding protein and activator protein-1 elements in macrophages. Kim, Y.M., Im, J.Y., Han, S.H., Kang, H.S., Choi, I. J. Immunol. (2000) [Pubmed]
  17. LPS regulates a set of genes in primary murine macrophages by antagonising CSF-1 action. Sester, D.P., Trieu, A., Brion, K., Schroder, K., Ravasi, T., Robinson, J.A., McDonald, R.C., Ripoll, V., Wells, C.A., Suzuki, H., Hayashizaki, Y., Stacey, K.J., Hume, D.A., Sweet, M.J. Immunobiology (2005) [Pubmed]
  18. ICSBP/IRF-8 inhibits mitogenic activity of p210 Bcr/Abl in differentiating myeloid progenitor cells. Tamura, T., Kong, H.J., Tunyaplin, C., Tsujimura, H., Calame, K., Ozato, K. Blood (2003) [Pubmed]
  19. AML1-ETO inhibits maturation of multiple lymphohematopoietic lineages and induces myeloblast transformation in synergy with ICSBP deficiency. Schwieger, M., Löhler, J., Friel, J., Scheller, M., Horak, I., Stocking, C. J. Exp. Med. (2002) [Pubmed]
  20. Regulation of apoptosis in myeloid cells by interferon consensus sequence-binding protein. Gabriele, L., Phung, J., Fukumoto, J., Segal, D., Wang, I.M., Giannakakou, P., Giese, N.A., Ozato, K., Morse, H.C. J. Exp. Med. (1999) [Pubmed]
  21. Essential role for ICSBP in the in vivo development of murine CD8alpha + dendritic cells. Aliberti, J., Schulz, O., Pennington, D.J., Tsujimura, H., Reis e Sousa, C., Ozato, K., Sher, A. Blood (2003) [Pubmed]
  22. Interferon consensus sequence binding protein confers resistance against Yersinia enterocolitica. Hein, J., Kempf, V.A., Diebold, J., Bücheler, N., Preger, S., Horak, I., Sing, A., Kramer, U., Autenrieth, I.B. Infect. Immun. (2000) [Pubmed]
  23. Differential expression of inducible nitric oxide synthase and IL-12 between peritoneal and splenic macrophages stimulated with LPS plus IFN-gamma is associated with the activation of extracellular signal-related kinase. Zhu, Y.N., Yang, Y.F., Ono, S., Zhong, X.G., Feng, Y.H., Ren, Y.X., Ni, J., Fu, Y.F., Tang, W., Zuo, J.P. Int. Immunol. (2006) [Pubmed]
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