Expression regulation and function of NLRC5
The NOD like receptors (NLRs), a class of intracellular receptors that respond to pathogen attack or cellular stress, have gained increasing attention. NLRC5, the largest member of the NLR protein family, has recently been identified as a critical regulator of immune responses. While NLRC5 is constitutively and widely expressed, it can be dramatically induced by interferons during pathogen infections. Both in vitro and in vivo studies have demonstrated that NLRC5 is a specific and master regulator of major mistocompatibility complex (MHC) class I genes as well as related genes involved in MHC class I antigen presentation. The expression of MHC class I genes is regulated by NLRC5 in coordination with the RFX components through an enhanceosome-dependent manner. And the involvement of NLRC5 in MHC class I mediated CD8+ T cell activation, proliferation and cytotoxicity is proved to be critical for host defense against intracellular bacterial infections. Nevertheless, the role of NLRC5 in innate immunity remains to be further explored. Here, we review the research advances on the structure, expression regulation and function of NLRC5.
KeywordsNLR NLRC5 MHC Class I
- Allen, I.C., Wilson, J.E., Schneider, M., Lich, J.D., Roberts, R.A., Arthur, J.C., Woodford, R.M., Davis, B.K., Uronis, J.M., Herfarth, H.H., et al. (2012). NLRP12 suppresses colon inflammation and tumorigenesis through the negative regulation of noncanonical NF-kappaB signaling. Immunity 36, 742–754.CrossRefGoogle Scholar
- Hake, S.B., Masternak, K., Kammerbauer, C., Janzen, C., Reith, W., and Steimle, V. (2000). CIITA leucine-rich repeats control nuclear localization, in vivo recruitment to the major histocompatibility complex (MHC) class II enhanceosome, and MHC class II gene transactivation. Mol Cell Biol 20, 7716–7725.CrossRefGoogle Scholar
- Kuenzel, S., Till, A., Winkler, M., Hasler, R., Lipinski, S., Jung, S., Grotzinger, J., Fickenscher, H., Schreiber, S., and Rosenstiel, P. (2010). The nucleotide-binding oligomerization domain-like receptor NLRC5 is involved in IFN-dependent antiviral immune responses. J Immunol 184, 1990–2000.CrossRefGoogle Scholar
- Schneider, M., Zimmermann, A.G., Roberts, R.A., Zhang, L., Swanson, K.V., Wen, H., Davis, B.K., Allen, I.C., Holl, E.K., Ye, Z., et al. (2012). The innate immune sensor NLRC3 attenuates Toll-like receptor signaling via modification of the signaling adaptor TRAF6 and transcription factor NF-kappaB. Nat Immunol 13, 823–831.CrossRefGoogle Scholar
- Staehli, F., Ludigs, K., Heinz, L.X., Seguin-Estevez, Q., Ferrero, I., Braun, M., Schroder, K., Rebsamen, M., Tardivel, A., Mattmann, C., et al. (2012). NLRC5 deficiency selectively impairs MHC class I-dependent lymphocyte killing by cytotoxic T cells. J Immunol 188, 3820–3828.CrossRefGoogle Scholar