Regulation of mouse inducible costimulator (ICOS) expression by Fyn-NFATc2 and ERK signaling in T cells - PubMed (original) (raw)
. 2006 Sep 29;281(39):28666-78.
doi: 10.1074/jbc.M604081200. Epub 2006 Jul 31.
Affiliations
- PMID: 16880206
- DOI: 10.1074/jbc.M604081200
Free article
Regulation of mouse inducible costimulator (ICOS) expression by Fyn-NFATc2 and ERK signaling in T cells
Andy Hee-Meng Tan et al. J Biol Chem. 2006.
Free article
Abstract
The inducible costimulator (ICOS), a member of the CD28 family of costimulatory molecules, is rapidly induced upon T cell activation. Although the critical role of ICOS in costimulating T cell responses is well documented, little is known of the intracellular signaling pathways and mechanisms that regulate ICOS expression. Here, we report that Fyn, NFAT, and ERK signaling influence ICOS expression as various chemical inhibitors, such as PP2 that targets Src kinases, U0126 that targets MEK1/2, and cyclosporin A or FK506 that targets calcineurin and thereby affects NFAT, attenuate T cell receptor-mediated ICOS induction. Moreover, ectopic expression of NFATc2 or a constitutively active MEK2 amplifies ICOS transcription and transactivates a 288-bp core region of the icos promoter in luciferase reporter assays. We also identify a site on the icos promoter that is sensitive to ERK signaling and further show that NFATc2 can bind the icos promoter in vivo and that this binding is diminished when Fyn signaling is ablated. The normal activation of ERK but reduced nuclear translocation of NFATc2 in Fyn(-/-) CD4(+) T cells further suggest that Fyn and NFATc2 act in a common axis, separate from that involving ERK, to drive ICOS transcription. Taken together, our findings indicate that Fyn-calcineurin-NFATc2 and MEK2-ERK1/2 are two independent signaling pathways that cooperate to control T cell receptor-mediated ICOS induction.
Similar articles
- T helper cell-specific regulation of inducible costimulator expression via distinct mechanisms mediated by T-bet and GATA-3.
Tan AH, Goh SY, Wong SC, Lam KP. Tan AH, et al. J Biol Chem. 2008 Jan 4;283(1):128-136. doi: 10.1074/jbc.M707693200. Epub 2007 Nov 6. J Biol Chem. 2008. PMID: 17986443 - Suppression of T cell costimulator ICOS by Delta9-tetrahydrocannabinol.
Lu H, Kaplan BL, Ngaotepprutaram T, Kaminski NE. Lu H, et al. J Leukoc Biol. 2009 Feb;85(2):322-9. doi: 10.1189/jlb.0608390. Epub 2008 Nov 6. J Leukoc Biol. 2009. PMID: 18988696 Free PMC article. - A single amino acid alteration in cytoplasmic domain determines IL-2 promoter activation by ligation of CD28 but not inducible costimulator (ICOS).
Harada Y, Ohgai D, Watanabe R, Okano K, Koiwai O, Tanabe K, Toma H, Altman A, Abe R. Harada Y, et al. J Exp Med. 2003 Jan 20;197(2):257-62. doi: 10.1084/jem.20021305. J Exp Med. 2003. PMID: 12538664 Free PMC article. - Regulation of CD4 T cell activation and effector function by inducible costimulator (ICOS).
Simpson TR, Quezada SA, Allison JP. Simpson TR, et al. Curr Opin Immunol. 2010 Jun;22(3):326-32. doi: 10.1016/j.coi.2010.01.001. Epub 2010 Jan 29. Curr Opin Immunol. 2010. PMID: 20116985 Review.
Cited by
- Chitinase-3-like 1 regulates TH2 cells, TFH cells and IgE responses to helminth infection.
Curtiss ML, Rosenberg AF, Scharer CD, Mousseau B, Benavides NAB, Bradley JE, León B, Steele C, Randall TD, Lund FE. Curtiss ML, et al. Front Immunol. 2023 Jul 27;14:1158493. doi: 10.3389/fimmu.2023.1158493. eCollection 2023. Front Immunol. 2023. PMID: 37575256 Free PMC article. - Neglected, yet significant role of FOXP1 in T-cell quiescence, differentiation and exhaustion.
Kaminskiy Y, Kuznetsova V, Kudriaeva A, Zmievskaya E, Bulatov E. Kaminskiy Y, et al. Front Immunol. 2022 Oct 4;13:971045. doi: 10.3389/fimmu.2022.971045. eCollection 2022. Front Immunol. 2022. PMID: 36268015 Free PMC article. Review. - The Differentiation and Maintenance of SARS-CoV-2-Specific Follicular Helper T Cells.
Wang Y, Tian Q, Ye L. Wang Y, et al. Front Cell Infect Microbiol. 2022 Jul 14;12:953022. doi: 10.3389/fcimb.2022.953022. eCollection 2022. Front Cell Infect Microbiol. 2022. PMID: 35909969 Free PMC article. Review. - Disrupting Roquin-1 interaction with Regnase-1 induces autoimmunity and enhances antitumor responses.
Behrens G, Edelmann SL, Raj T, Kronbeck N, Monecke T, Davydova E, Wong EH, Kifinger L, Giesert F, Kirmaier ME, Hohn C, de Jonge LS, Pisfil MG, Fu M, Theurich S, Feske S, Kawakami N, Wurst W, Niessing D, Heissmeyer V. Behrens G, et al. Nat Immunol. 2021 Dec;22(12):1563-1576. doi: 10.1038/s41590-021-01064-3. Epub 2021 Nov 22. Nat Immunol. 2021. PMID: 34811541 Free PMC article. - B Cells Drive Autoimmunity in Mice with CD28-Deficient Regulatory T Cells.
Zhang R, Sage PT, Finn K, Huynh A, Blazar BR, Marangoni F, Mempel TR, Sharpe AH, Turka LA. Zhang R, et al. J Immunol. 2017 Dec 15;199(12):3972-3980. doi: 10.4049/jimmunol.1700409. Epub 2017 Nov 1. J Immunol. 2017. PMID: 29093061 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Molecular Biology Databases
Research Materials
Miscellaneous