Abstract
Schnurri (Shn) is a large zinc-finger containing protein, which plays a critical role in cell growth, signal transduction and lymphocyte development. There are three orthologues (Shn-1, Shn-2 and Shn-3) in vertebrates. In Shn-2-deficient mice, the activation of NF-κB in CD4 T cells is upregulated and their ability to differentiate into Th2 cells is enhanced in part through the increased expression of GATA3. Shn-2 is found to compete with p50 NF- κB for binding to a consensus NF-κB motif and inhibit the NF-κB-driven promoter activity. In addition, Th2-driven allergic airway inflammation was enhanced in Shn-2-deficient mice. Therefore, Shn-2 appears to negatively control the differentiation of Th2 cells and Th2 responses through the repression of NF-κB function. Memory Th1/Th2 cells are not properly generated from Shn-2-deficient effector Th1/Th2 cells. The expression levels of CD69 and the number of apoptotic cells are selectively increased in Shn-2-deficient Th1/Th2 cells when they are transferred into syngeneic host animals, in which memory Th1/Th2 cells are generated within a month. In addition, an increased susceptibility to apoptotic cell death is also observed in vitro accompanied with the increased expression of FasL, one of the NF-κB-dependent genes. Th2 effector cells overexpressing the p65 subunit of NF-κB demonstrate a decreased cell survival particularly in the lymph node. These results indicate that Shn-2-mediated repression of NF-κB is required for cell survival and the successful generation of memory Th1/Th2 cells. This may point to the possibility that after antigen clearance the recovery of the quiescent state in effector Th cells is required for the generation of memory Th cells. A repressor molecule Shn-2 plays an important role in this process.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Ansel KM, Djuretic I, Tanasa B et al. Regulation of Th2 differentiation and Il4 locus accessibility. Annu Rev Immunol 2006; 24:607–656.
Mowen KA, Glimcher LH. Signaling pathways in Th2 development. Immunol Rev 2004; 202:203–222.
Szabo SJ, Sullivan BM, Peng SL et al. Molecular mechanisms regulating Th1 immune responses. Annu Rev Immunol 2003; 21:713–758.
Ivanov II, McKenzie BS, Zhou L et al. The orphan nuclear receptor ROR γ t directs the differentiation program of proinflammatory IL-17 +T helper cells. Cell 2006; 126(6):1121–1133.
Nakayama T, Yamashita M. Initiation and maintenance of Th2 cell identity. Curr Opin Immunol 2008; 20(3): 265–271.
Marrack P, Kappler J. Control of T-cell viability. Annu Rev Immunol 2004; 22:765–787.
Affolter M, Marty T, Vigano MA et al. Nuclear interpretation of Dpp signaling in Drosophila. EMBO J 2001; 20(13):3298–3305.
Arora K, Dai H, Kazuko SG et al. The Drosophila schnurri gene acts in the Dpp/TGF β signaling pathway and encodes a transcription factor homologous to the human MBP family. Cell 1995; 81(5):781–790.
Staehling-Hampton K, Laughon AS, Hoffmann FM. A Drosophila protein related to the human zinc finger transcription factor PRDII/MBPI/HIV-EP1 is required for dpp signaling. Development 1995; 121(10): 3393–3403.
Kingsley DM. The TGF-β superfamily: new members, new receptors and new genetic tests of function in different organisms. Genes Dev 1994; 8(2):133–146.
Wu LC, Mak CH, Dear N et al. Molecular cloning of a zinc finger protein which binds to the heptamer of the signal sequence for V(D)J recombination. Nucleic Acids Res 1993; 21(22):5067–5073.
Hong JW, Allen CE, Wu LC. Inhibition of NF-κB by ZAS3, a zinc-finger protein that also binds to the κB motif. Proc Natl Acad Sci USA 2003; 100(21):12301–12306.
Oukka M, Kim ST, Lugo G et al. A mammalian homolog of Drosophila schnurri, KRC, regulates TNF receptor-driven responses and interacts with TRAF2. Mol Cell 2002; 9(1):121–131.
Oukka M, Wein MN, Glimcher LH. Schnurri-3 (KRC) Interacts with c-Jun to Regulate the IL-2 Gene in T-Cells. J Exp Med 2004; 199(1):15–24.
Jones DC, Wein MN, Oukka M et al. Regulation of adult bone mass by the zinc finger adapter protein Schnurri-3. Science 2006; 312(5777):1223–1227.
Allen CE, Muthusamy N, Weisbrode SE et al. Developmental anomalies and neoplasia in animals and cells deficient in the large zinc finger protein KRC. Genes Chromosomes Cancer 2002; 35(4):287–298.
Makino R, Akiyama K, Yasuda J et al. Cloning and characterization of a c-myc intron binding protein (MIBP1). Nucleic Acids Res 1994; 22(25):5679–5685.
Ron D, Brasier AR, Habener JF. Angiotensinogen gene-inducible enhancer-binding protein 1, a member of a new family of large nuclear proteins that recognize nuclear factor κB-binding sites through a zinc finger motif. Mol Cell Biol 1991; 11(5):2887–2895.
Campbell DB, Levitt P. Regionally restricted expression of the transcription factor c-myc intron 1 binding protein during brain development. J Comp Neurol 2003; 467(4):581–592.
Takagi T, Harada J, Ishii S. Murine Schnurri-2 is required for positive selection of thymocytes. Nat Immunol 2001; 2(11):1048–1053.
Kimura MY, Hosokawa H, Yamashita M et al. Regulation of T helper type 2 cell differentiation by murine Schnurri-2. J Exp Med 2005; 201(3):397–408.
Saita Y, Takagi T, Kitahara K et al. Lack of Schnurri-2 expression associates with reduced bone remodeling and osteopenia. J Biol Chem 2007; 282(17):12907–12915.
Jin W, Takagi T, Kanesashi SN et al. Schnurri-2 controls BMP-dependent adipogenesis via interaction with Smad proteins. Dev Cell 2006; 10(4):461–471.
Iwamura C, Kimura MY, Shinoda K et al. Schnurri-2 regulates Th2-dependent airway inflammation and airway hyperresponsiveness. Int Immunol 2007; 19(6):755–762.
Zhang DH, Cohn L, Ray P et al. Transcription factor GATA-3 is differentially expressed in murine Th1 and Th2 cells and controls Th2-specific expression of the interleukin-5 gene. J Biol Chem 1997; 272(34): 21597–21603.
Zheng W, Flavell RA. The transcription factor GATA-3 is necessary and sufficient for Th2 cytokine gene expression in CD4 T-cells. Cell 1997; 89(4):587–596.
Takeda K, Tanaka T, Shi W et al. Essential role of Stat6 in IL-4 signalling. Nature 1996; 380(6575): 627–630.
Yamashita M, Kimura M, Kubo M et al. T-cell antigen receptor-mediated activation of the Ras/ mitogen-activated protein kinase pathway controls interleukin 4 receptor function and type-2 helper T-cell differentiation. Proc Natl Acad Sci USA 1999; 96(3):1024–1029.
Yamashita M, Katsumata M, Iwashima M et al. T-cell receptor-induced calcineurin activation regulates T helper type 2 cell development by modifying the interleukin 4 receptor signaling complex. J Exp Med 2000; 191: 1869–1879.
Das J, Chen CH, Yang L et al. A critical role for NF-κB in GATA3 expression and T H2 differentiation in allergic airway inflammation. Nat Immunol 2001; 2(1):45–50.
Stevens L, Htut TM, White D et al. Involvement of GATA3 in protein kinase C θ-induced Th2 cytokine expression. Eur J Immunol 2006; 36(12):3305–3314.
Yamashita M, Shinnakasu R, Nigo Y et al. Interleukin (IL)-4-independent maintenance of histone modification of the IL-4 gene loci in memory Th2 cells. J Biol Chem 2004; 279(38):39454–39464.
Zanetti M, Franchini G. T-cell memory and protective immunity by vaccination: is more better? Trends Immunol 2006; 27(11):511–517.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2010 Landes Bioscience and Springer Science+Business Media
About this chapter
Cite this chapter
Nakayama, T., Kimura, M.Y. (2010). Memory Th1/Th2 Cell Generation Controlled by Schnurri-2. In: Zanetti, M., Schoenberger, S.P. (eds) Memory T Cells. Advances in Experimental Medicine and Biology, vol 684. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-6451-9_1
Download citation
DOI: https://doi.org/10.1007/978-1-4419-6451-9_1
Publisher Name: Springer, New York, NY
Print ISBN: 978-1-4419-6450-2
Online ISBN: 978-1-4419-6451-9
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)