Transcriptional mechanisms underlying lymphocyte tolerance
- PMID:12086671
- DOI: 10.1016/s0092-8674(02)00767-5
Transcriptional mechanisms underlying lymphocyte tolerance
Abstract
In lymphocytes, integration of Ca2+ and other signaling pathways results in productive activation, while unopposed Ca2+ signaling leads to tolerance or anergy. We show that the Ca2+-regulated transcription factor NFAT has an integral role in both aspects of lymphocyte function. Ca2+/calcineurin signaling induces a limited set of anergy-associated genes, distinct from genes induced in the productive immune response; these genes are upregulated in vivo in tolerant T cells and are largely NFAT dependent. T cells lacking NFAT1 are resistant to anergy induction; conversely, NFAT1 induces T cell anergy if prevented from interacting with its transcriptional partner AP-1 (Fos/Jun). Thus, in the absence of AP-1, NFAT imposes a genetic program of lymphocyte anergy that counters the program of productive activation mediated by the cooperative NFAT:AP-1 complex.
Similar articles
- A molecular dissection of lymphocyte unresponsiveness induced by sustained calcium signalling.Heissmeyer V, Macián F, Varma R, Im SH, García-Cozar F, Horton HF, Byrne MC, Feske S, Venuprasad K, Gu H, Liu YC, Dustin ML, Rao A.Heissmeyer V, et al.Novartis Found Symp. 2005;267:165-74; discussion 174-9.Novartis Found Symp. 2005.PMID:15999806
- Activation and deactivation of gene expression by Ca2+/calcineurin-NFAT-mediated signaling.Im SH, Rao A.Im SH, et al.Mol Cells. 2004 Aug 31;18(1):1-9.Mol Cells. 2004.PMID:15359117Review.
- Alterations in transcription factor binding at the IL-2 promoter region in anergized human CD4+ T lymphocytes.Heisel O, Keown P.Heisel O, et al.Transplantation. 2001 Oct 27;72(8):1416-22. doi: 10.1097/00007890-200110270-00015.Transplantation. 2001.PMID:11685114
- Impaired AP-1 dimers and NFAT complex formation in immature thymocytes during in vivo glucocorticoid-induced apoptosis.Wisniewska M, Pyrzynska B, Kaminska B.Wisniewska M, et al.Cell Biol Int. 2004;28(11):773-80. doi: 10.1016/j.cellbi.2004.07.008.Cell Biol Int. 2004.PMID:15563399
- Partners in transcription: NFAT and AP-1.Macián F, López-Rodríguez C, Rao A.Macián F, et al.Oncogene. 2001 Apr 30;20(19):2476-89. doi: 10.1038/sj.onc.1204386.Oncogene. 2001.PMID:11402342Review.
Cited by
- Cbl-b deficiency prevents functional but not phenotypic T cell anergy.Nguyen TTT, Wang ZE, Shen L, Schroeder A, Eckalbar W, Weiss A.Nguyen TTT, et al.J Exp Med. 2021 Jul 5;218(7):e20202477. doi: 10.1084/jem.20202477. Epub 2021 May 11.J Exp Med. 2021.PMID:33974042Free PMC article.
- Rapid in vitro generation of bona fide exhausted CD8+ T cells is accompanied by Tcf7 promotor methylation.Zhao M, Kiernan CH, Stairiker CJ, Hope JL, Leon LG, van Meurs M, Brouwers-Haspels I, Boers R, Boers J, Gribnau J, van IJcken WFJ, Bindels EM, Hoogenboezem RM, Erkeland SJ, Mueller YM, Katsikis PD.Zhao M, et al.PLoS Pathog. 2020 Jun 24;16(6):e1008555. doi: 10.1371/journal.ppat.1008555. eCollection 2020 Jun.PLoS Pathog. 2020.PMID:32579593Free PMC article.
- Feeding an army: The metabolism of T cells in activation, anergy, and exhaustion.Delgoffe GM, Powell JD.Delgoffe GM, et al.Mol Immunol. 2015 Dec;68(2 Pt C):492-6. doi: 10.1016/j.molimm.2015.07.026.Mol Immunol. 2015.PMID:26256793Free PMC article.Review.
- Induction of T-cell activation or anergy determined by the combination of intensity and duration of T-cell receptor stimulation, and sequential induction in an individual cell.Yamamoto T, Hattori M, Yoshida T.Yamamoto T, et al.Immunology. 2007 Jul;121(3):383-91. doi: 10.1111/j.1365-2567.2007.02586.x. Epub 2007 Mar 22.Immunology. 2007.PMID:17376194Free PMC article.
- Cyclin-dependent kinases: molecular switches controlling anergy and potential therapeutic targets for tolerance.Wells AD.Wells AD.Semin Immunol. 2007 Jun;19(3):173-9. doi: 10.1016/j.smim.2007.02.009. Epub 2007 Mar 23.Semin Immunol. 2007.PMID:17383195Free PMC article.Review.
Publication types
MeSH terms
Substances
Related information
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources
Miscellaneous