Differential Interleukin-2 Transcription Kinetics Render Mouse but Not Human T Cells Vulnerable to Splicing Inhibition Early after Activation

REFERENCES

• Guy CS, Vignali KM, Temirov J, Bettini ML, Overacre AE, Smeltzer M, Zhang H, Huppa JB, Tsai YH, Lobry C, Xie J, Dempsey PJ, Crawford HC, Aifantis I, Davis MM, Vignali DA. 2013. Distinct TCR signaling pathways drive proliferation and cytokine production in T cells. Nat Immunol 14:262–270. https://doi.org/10.1038/ni.2538.
   PubMed Web of Science ®Google Scholar
• Hamilton SE, Jameson SC. 2012. CD8 T cell quiescence revisited. Trends Immunol 33:224–230. https://doi.org/10.1016/j.it.2012.01.007.
   PubMed Web of Science ®Google Scholar
• Zhu J, Yamane H, Paul WE. 2010. Differentiation of effector CD4 T cell populations. Annu Rev Immunol 28:445–489. https://doi.org/10.1146/annurev-immunol-030409-101212.
   PubMed Web of Science ®Google Scholar
• Pennock ND, White JT, Cross EW, Cheney EE, Tamburini BA, Kedl RM. 2013. T cell responses: naive to memory and everything in between. Adv Physiol Educ 37:273–283. https://doi.org/10.1152/advan.00066.2013.
   PubMed Web of Science ®Google Scholar
• Fiedler W, Sykora KW, Welte K, Kolitz JE, Cunningham-Rundles C, Holloway K, Miller GA, Souza L, Mertelsmann R. 1987. T-cell activation defect in common variable immunodeficiency: restoration by phorbol myristate acetate (PMA) or allogeneic macrophages. Clin Immunol Immunopathol 44:206–218. https://doi.org/10.1016/0090-1229(87)90066-3.
   PubMedGoogle Scholar
• Fischer MB, Hauber I, Eggenbauer H, Thon V, Vogel E, Schaffer E, Lokaj J, Litzman J, Wolf HM, Mannhalter JW. 1994. A defect in the early phase of T-cell receptor-mediated T-cell activation in patients with common variable immunodeficiency. Blood 84:4234–4241.
   PubMed Web of Science ®Google Scholar
• Scotese I, Gaetaniello L, Matarese G, Lecora M, Racioppi L, Pignata C. 1998. T cell activation deficiency associated with an aberrant pattern of protein tyrosine phosphorylation after CD3 perturbation in Down's syndrome. Pediatr Res 44:252–258. https://doi.org/10.1203/00006450-199808000-00019.
   PubMed Web of Science ®Google Scholar
• Shier P, Ngo K, Fung-Leung WP. 1999. Defective CD8+ T cell activation and cytolytic function in the absence of LFA-1 cannot be restored by increased TCR signaling. J Immunol 163:4826–4832.
   PubMed Web of Science ®Google Scholar
• Davari K, Lichti J, Gallus C, Greulich F, Uhlenhaut NH, Heinig M, Friedel CC, Glasmacher E. 2017. Rapid genome-wide recruitment of RNA polymerase II drives transcription, splicing, and translation events during T cell responses. Cell Rep 19:643–654. https://doi.org/10.1016/j.celrep.2017.03.069.
   PubMed Web of Science ®Google Scholar
• Tan H, Yang K, Li Y, Shaw TI, Wang Y, Blanco DB, Wang X, Cho JH, Wang H, Rankin S, Guy C, Peng J, Chi H. 2017. Integrative proteomics and phosphoproteomics profiling reveals dynamic signaling networks and bioenergetics pathways underlying T cell activation. Immunity 46:488–503. https://doi.org/10.1016/j.immuni.2017.02.010.
   PubMed Web of Science ®Google Scholar
• Black DL. 2000. Protein diversity from alternative splicing: a challenge for bioinformatics and post-genome biology. Cell 103:367–370. https://doi.org/10.1016/S0092-8674(00)00128-8.
   PubMed Web of Science ®Google Scholar
• Lynch KW. 2004. Consequences of regulated pre-mRNA splicing in the immune system. Nat Rev Immunol 4:931–940. https://doi.org/10.1038/nri1497.
   PubMed Web of Science ®Google Scholar
• Gaudreau MC, Heyd F, Bastien R, Wilhelm B, Moroy T. 2012. Alternative splicing controlled by heterogeneous nuclear ribonucleoprotein L regulates development, proliferation, and migration of thymic pre-T cells. J Immunol 188:5377–5388. https://doi.org/10.4049/jimmunol.1103142.
   PubMed Web of Science ®Google Scholar
• Mallory MJ, Allon SJ, Qiu J, Gazzara MR, Tapescu I, Martinez NM, Fu XD, Lynch KW. 2015. Induced transcription and stability of CELF2 mRNA drives widespread alternative splicing during T-cell signaling. Proc Natl Acad Sci U S A 112:E2139–E2148. https://doi.org/10.1073/pnas.1423695112.
   PubMed Web of Science ®Google Scholar
• Michel M, Wilhelmi I, Schultz AS, Preussner M, Heyd F. 2014. Activation-induced tumor necrosis factor receptor-associated factor 3 (Traf3) alternative splicing controls the noncanonical nuclear factor kappaB pathway and chemokine expression in human T cells. J Biol Chem 289:13651–13660. https://doi.org/10.1074/jbc.M113.526269.
   PubMed Web of Science ®Google Scholar
• Rajani DK, Walch M, Martinvalet D, Thomas MP, Lieberman J. 2012. Alterations in RNA processing during immune-mediated programmed cell death. Proc Natl Acad Sci U S A 109:8688–8693. https://doi.org/10.1073/pnas.1201327109.
   PubMed Web of Science ®Google Scholar
• Weg-Remers S, Ponta H, Herrlich P, König H. 2001. Regulation of alternative pre-mRNA splicing by the ERK MAP-kinase pathway. EMBO J 20:4194–4203. https://doi.org/10.1093/emboj/20.15.4194.
   PubMed Web of Science ®Google Scholar
• Wilhelmi I, Kanski R, Neumann A, Herdt O, Hoff F, Jacob R, Preußner M, Heyd F. 2016. Sec16 alternative splicing dynamically controls COPII transport efficiency. Nat Commun 7:12347. https://doi.org/10.1038/ncomms12347.
   PubMed Web of Science ®Google Scholar
• Butte MJ, Lee SJ, Jesneck J, Keir ME, Haining WN, Sharpe AH. 2012. CD28 costimulation regulates genome-wide effects on alternative splicing. PLoS One 7:e40032. https://doi.org/10.1371/journal.pone.0040032.
   Google Scholar
• Grigoryev YA, Kurian SM, Nakorchevskiy AA, Burke JP, Campbell D, Head SR, Deng J, Kantor AB, Yates JR, III, Salomon DR. 2009. Genome-wide analysis of immune activation in human T and B cells reveals distinct classes of alternatively spliced genes. PLoS One 4:e7906. https://doi.org/10.1371/journal.pone.0007906.
   PubMed Web of Science ®Google Scholar
• Ip JY, Tong A, Pan Q, Topp JD, Blencowe BJ, Lynch KW. 2007. Global analysis of alternative splicing during T-cell activation. RNA 13:563–572. https://doi.org/10.1261/rna.457207.
   PubMed Web of Science ®Google Scholar
• Martinez NM, Pan Q, Cole BS, Yarosh CA, Babcock GA, Heyd F, Zhu W, Ajith S, Blencowe BJ, Lynch KW. 2012. Alternative splicing networks regulated by signaling in human T cells. RNA 18:1029–1040. https://doi.org/10.1261/rna.032243.112.
   PubMed Web of Science ®Google Scholar
• Pearson-White S, McDuffie M. 2003. Defective T-cell activation is associated with augmented transforming growth factor beta sensitivity in mice with mutations in the Sno gene. Mol Cell Biol 23:5446–5459. https://doi.org/10.1128/mcb.23.15.5446-5459.2003.
   PubMed Web of Science ®Google Scholar
• Duke RC, Cohen JJ. 1986. IL-2 addiction: withdrawal of growth factor activates a suicide program in dependent T cells. Lymphokine Res 5:289–299.
   PubMedGoogle Scholar
• Collins S, Lutz MA, Zarek PE, Anders RA, Kersh GJ, Powell JD. 2008. Opposing regulation of T cell function by Egr-1/NAB2 and Egr-2/Egr-3. Eur J Immunol 38:528–536. https://doi.org/10.1002/eji.200737157.
   PubMed Web of Science ®Google Scholar
• Collins S, Wolfraim LA, Drake CG, Horton MR, Powell JD. 2006. Cutting edge: TCR-induced NAB2 enhances T cell function by coactivating IL-2 transcription. J Immunol 177:8301–8305. https://doi.org/10.4049/jimmunol.177.12.8301.
   PubMed Web of Science ®Google Scholar
• Kumbrink J, Gerlinger M, Johnson JP. 2005. Egr-1 induces the expression of its corepressor Nab2 by activation of the Nab2 promoter thereby establishing a negative feedback loop. J Biol Chem 280:42785–42793. https://doi.org/10.1074/jbc.M511079200.
   PubMed Web of Science ®Google Scholar
• Kumbrink J, Kirsch KH, Johnson JP. 2010. EGR1, EGR2, and EGR3 activate the expression of their coregulator NAB2 establishing a negative feedback loop in cells of neuroectodermal and epithelial origin. J Cell Biochem 111:207–217. https://doi.org/10.1002/jcb.22690.
   PubMed Web of Science ®Google Scholar
• Bhattacharyya S, Wei J, Melichian DS, Milbrandt J, Takehara K, Varga J. 2009. The transcriptional cofactor Nab2 is induced by TGF-beta and suppresses fibroblast activation: physiological roles and impaired expression in scleroderma. PLoS One 4:e7620. https://doi.org/10.1371/journal.pone.0007620.
   Google Scholar
• Svaren J, Sevetson BR, Apel ED, Zimonjic DB, Popescu NC, Milbrandt J. 1996. NAB2, a corepressor of NGFI-A (Egr-1) and Krox20, is induced by proliferative and differentiative stimuli. Mol Cell Biol 16:3545–3553. https://doi.org/10.1128/mcb.16.7.3545.
   PubMed Web of Science ®Google Scholar
• Iacobelli M, Rohwer F, Shanahan P, Quiroz JA, McGuire KL. 1999. IL-2-mediated cell cycle progression and inhibition of apoptosis does not require NF-kappa B or activating protein-1 activation in primary human T cells. J Immunol 162:3308–3315.
   PubMed Web of Science ®Google Scholar
• Sereti I, Gea-Banacloche J, Kan MY, Hallahan CW, Lane HC. 2000. Interleukin 2 leads to dose-dependent expression of the alpha chain of the IL-2 receptor on CD25-negative T lymphocytes in the absence of exogenous antigenic stimulation. Clin Immunol 97:266–276. https://doi.org/10.1006/clim.2000.4929.
   PubMed Web of Science ®Google Scholar
• Burchill MA, Yang J, Vang KB, Farrar MA. 2007. Interleukin-2 receptor signaling in regulatory T cell development and homeostasis. Immunol Lett 114:1–8. https://doi.org/10.1016/j.imlet.2007.08.005.
   PubMed Web of Science ®Google Scholar
• Liao W, Lin JX, Leonard WJ. 2013. Interleukin-2 at the crossroads of effector responses, tolerance, and immunotherapy. Immunity 38:13–25. https://doi.org/10.1016/j.immuni.2013.01.004.
   PubMed Web of Science ®Google Scholar
• Malek TR. 2008. The biology of interleukin-2. Annu Rev Immunol 26:453–479. https://doi.org/10.1146/annurev.immunol.26.021607.090357.
   PubMed Web of Science ®Google Scholar
• Malek TR, Castro I. 2010. Interleukin-2 receptor signaling: at the interface between tolerance and immunity. Immunity 33:153–165. https://doi.org/10.1016/j.immuni.2010.08.004.
   PubMed Web of Science ®Google Scholar
• Paetkau V. 1985. Molecular biology of interleukin 2. Can J Biochem Cell Biol 63:691–699. https://doi.org/10.1139/o85-086.
   PubMedGoogle Scholar
• Ross SH, Cantrell DA. 2018. Signaling and function of interleukin-2 in T lymphocytes. Annu Rev Immunol 36:411–433. https://doi.org/10.1146/annurev-immunol-042617-053352.
   PubMed Web of Science ®Google Scholar
• Salerno F, Paolini NA, Stark R, von Lindern M, Wolkers MC. 2017. Distinct PKC-mediated posttranscriptional events set cytokine production kinetics in CD8(+) T cells. Proc Natl Acad Sci U S A 114:9677–9682. https://doi.org/10.1073/pnas.1704227114.
   PubMed Web of Science ®Google Scholar
• Sojka DK, Bruniquel D, Schwartz RH, Singh NJ. 2004. IL-2 secretion by CD4+ T cells in vivo is rapid, transient, and influenced by TCR-specific competition. J Immunol 172:6136–6143. https://doi.org/10.4049/jimmunol.172.10.6136.
   PubMed Web of Science ®Google Scholar
• Peter D, Jin SL, Conti M, Hatzelmann A, Zitt C. 2007. Differential expression and function of phosphodiesterase 4 (PDE4) subtypes in human primary CD4+ T cells: predominant role of PDE4D. J Immunol 178:4820–4831. https://doi.org/10.4049/jimmunol.178.8.4820.
   PubMed Web of Science ®Google Scholar
• Shimoyamada H, Yazawa T, Sato H, Okudela K, Ishii J, Sakaeda M, Kashiwagi K, Suzuki T, Mitsui H, Woo T, Tajiri M, Ohmori T, Ogura T, Masuda M, Oshiro H, Kitamura H. 2010. Early growth response-1 induces and enhances vascular endothelial growth factor-A expression in lung cancer cells. Am J Pathol 177:70–83. https://doi.org/10.2353/ajpath.2010.091164.
   PubMed Web of Science ®Google Scholar
• Adams KW, Kletsov S, Lamm RJ, Elman JS, Mullenbrock S, Cooper GM. 2017. Role for Egr1 in the transcriptional program associated with neuronal differentiation of PC12 cells. PLoS One 12:e0170076. https://doi.org/10.1371/journal.pone.0170076.
   Google Scholar
• Lucerna M, Mechtcheriakova D, Kadl A, Schabbauer G, Schafer R, Gruber F, Koshelnick Y, Muller HD, Issbrucker K, Clauss M, Binder BR, Hofer E. 2003. NAB2, a corepressor of EGR-1, inhibits vascular endothelial growth factor-mediated gene induction and angiogenic responses of endothelial cells. J Biol Chem 278:11433–11440. https://doi.org/10.1074/jbc.M204937200.
   PubMed Web of Science ®Google Scholar
• Herdt O, Neumann A, Timmermann B, Heyd F. 2017. The cancer-associated U2AF35 470A>G (Q157R) mutation creates an in-frame alternative 5′ splice site that impacts splicing regulation in Q157R patients. RNA 23:1796–1806. https://doi.org/10.1261/rna.061432.117.
   PubMed Web of Science ®Google Scholar
• Shen Y, Vignali P, Wang R. 2017. Rapid profiling cell cycle by flow cytometry using concurrent staining of DNA and mitotic markers. Bio Protoc 7:e2517. https://doi.org/10.21769/BioProtoc.2517.
   Google Scholar
• Preußner M, Goldammer G, Neumann A, Haltenhof T, Rautenstrauch P, Müller-McNicoll M, Heyd F. 2017. Body temperature cycles control rhythmic alternative splicing in mammals. Mol Cell 67:433–446.e4. https://doi.org/10.1016/j.molcel.2017.06.006.
   PubMed Web of Science ®Google Scholar
• Conrad T, Orom UA. 2017. Cellular fractionation and isolation of chromatin-associated RNA. Methods Mol Biol 1468:1–9. https://doi.org/10.1007/978-1-4939-4035-6_1.
   PubMedGoogle Scholar
• Dobin A, Davis CA, Schlesinger F, Drenkow J, Zaleski C, Jha S, Batut P, Chaisson M, Gingeras TR. 2013. STAR: ultrafast universal RNA-seq aligner. Bioinformatics 29:15–21. https://doi.org/10.1093/bioinformatics/bts635.
   PubMed Web of Science ®Google Scholar