Abstract
Dendritic cells (DCs) comprise a family of professional antigen-presenting cells responsible for the induction of primary immune responses. DCs are also important for the induction of immunological tolerance. Recent research has revealed that DC maturation is associated with activation of the NF-κB pathway. RelB, one of the five families of Rel proteins involved in the NF-κB pathway, plays a critical role in coordinating the terminal stages of DC maturation and has the ability to induce optimal Th1 T cell responses. DCs generated from mouse bone marrow can be silenced using siRNA specific for the target gene. Silencing RelB in DCs will result in the generation of immunoregulatory dendritic cells that inhibit allogenic T cell responses. The KLH-specific T cell response should also be inhibited after the RelB siRNA treatment. Furthermore, silencing the RelB gene in DCs can generate regulatory T cells. Administering donor-derived RelB-silencing DCs can prevent allograft rejection in murine heart transplantation.
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References
Banchereau, J., Briere, F., Caux, C., Davoust, J., Lebecque, S.and Liu, Y.J. et al. (2000) Immunobiology of dendritic cells. Annu. Rev. Immunol. 18, 767–811.
Reis e Sousa, C. (2006) Dendritic cells in a mature age. Nat. Rev. Immunol. 6(6), 476–483.
Xu, D.L., Liu, Y., Tan, J.M., Li, B., Zhong, C.P. and Zhang, X.H. et al. (2004) Marked prolongation of murine cardiac allograft survival using recipient immature dendritic cells loaded with donor-derived apoptotic cells. Scand. J. Immunol. 59(6), 536–544.
Wang, Q., Zhang, M., Ding, G., Liu, Y., Sun, Y., Wang, J. et al. (2003) Anti-ICAM-1 antibody and CTLA-4Ig synergistically enhance immature dendritic cells to induce donor-specific immune tolerance in vivo. Immunol. Lett. 90(1), 33–42.
Rescigno, M., Martino, M., Sutherland, C.L., Gold, M.R. and Ricciardi-Castagnoli P. (1998) Dendritic cell survival and maturation are regulated by different signaling pathways. J. Exp. Med. 188(11), 2175–2180.
Ardeshna, K.M., Pizzey, A.R., Devereux, S. and Khwaja, A. (2000) The PI3 kinase, p38 SAP kinase, and NF-kappaB signal transduction pathways are involved in the survival and maturation of lipopolysaccharide-stimulated human monocyte-derived dendritic cells. Blood 96(3), 1039–1046.
Caamano, J. and Hunter, C.A. (2002) NF-kappaB family of transcription factors: central regulators of innate and adaptive immune functions. Clin. Microbiol. Rev. 15(3), 414–429.
Wu, L., D’Amico, A., Winkel, K.D., Suter, M., Lo, D. and Shortman, K. (1998) RelB is essential for the development of myeloid-related CD8alpha− dendritic cells but not of lymphoid-related CD8alpha+ dendritic cells. Immunity 9(6), 839–847.
Cejas, P.J., Carlson, L.M., Kolonias, D., Zhang, J., Lindner, I. and Billadeau, D.D. et al. (2005) Regulation of RelB expression during the initiation of dendritic cell differentiation. Mol. Cell. Biol. 25(17), 7900–7916.
Burkly, L., Hession, C., Ogata, L., Reilly, C., Marconi, L.A. and Olson, D. et al. (1995) Expression of relB is required for the development of thymic medulla and dendritic cells. Nature 373(6514), 531–536.
Weih, F., Carrasco, D., Durham, S.K., Barton, D.S., Rizzo, C.A. and Ryseck, R.P. et al. (1995) Multiorgan inflammation and hematopoietic abnormalities in mice with a targeted disruption of RelB, a member of the NF-kappa B/Rel family. Cell 80(2), 331–340.
Zanetti, M., Castiglioni, P., Schoenberger, S. and Gerloni, M. (2003) The role of relB in regulating the adaptive immune response. Ann. N. Y. Acad. Sci. 987, 249–257.
Fire, A., Xu, S., Montgomery, M.K., Kostas, S.A., Driver, S.E. and Mello, C.C. (1998) Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans. Nature 391(6669), 806–811.
Elbashir, S.M., Harborth, J., Lendeckel, W., Yalcin, A., Weber, K. and Tuschl, T. (2001) Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells. Nature 411(6836), 494–498.
Hill, J.A., Ichim, T.E., Kusznieruk, K.P., Li, M., Huang, X. and Yan, X. et al. (2003) Immune modulation by silencing IL-12 production in dendritic cells using small interfering RNA. J. Immunol. 171(2), 691–696.
de Fougerolles, A., Vornlocher, H.P., Maraganore, J. and Lieberman, J. (2007) Interfering with disease: a progress report on siRNA-based therapeutics. Nat. Rev. Drug Discov. 6(6), 443–453.
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Zhang, X., Li, M., Min, WP. (2010). Preventing Immune Rejection Through Gene Silencing. In: Min, WP., Ichim, T. (eds) RNA Interference. Methods in Molecular Biology, vol 623. Humana Press. https://doi.org/10.1007/978-1-60761-588-0_23
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DOI: https://doi.org/10.1007/978-1-60761-588-0_23
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