A simple theoretical framework for understanding heterogeneous differentiation of CD4 + T cells

BMC Systems Biology

Volumn 6, Issue , 2012, Pages

  Hong, Tian ^a   Xing, Jianhua ^a   Li, Liwu ^a   Tyson, John J ^a  

^a VIRGINIA POLYTECHNIC INSTITUTE AND STATE UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ARTICLE; BIOLOGICAL MODEL; CD4+ T LYMPHOCYTE; CELL DIFFERENTIATION; CYTOLOGY; FEEDBACK SYSTEM; METABOLISM; SIGNAL TRANSDUCTION;

CD4-POSITIVE T-LYMPHOCYTES; CELL DIFFERENTIATION; FEEDBACK, PHYSIOLOGICAL; MODELS, BIOLOGICAL; SIGNAL TRANSDUCTION;

EID: 84862209563     PISSN: None     EISSN: 17520509     Source Type: Journal    
DOI: 10.1186/1752-0509-6-66     Document Type: Article

References (69)

1. Dranoff G, Jaffee E, Lazenby A, Golumbek P, Levitsky H, Brose K, Jackson V, Hamada H, Pardoll D, Mulligan RC. Vaccination with irradiated tumor cells engineered to secrete murine granulocyte-macrophage colony-stimulating factor stimulates potent, specific, and long-lasting anti-tumor immunity. Proc Natl Acad Sci U S A 1993, 90:3539-3543. 10.1073/pnas.90.8.3539, 46336, 8097319.
2. Moir S, Chun TW, Fauci AS. Pathogenic mechanisms of HIV disease. Annu Rev Pathol 2011, 6:223-248. 10.1146/annurev-pathol-011110-130254, 21034222.
3. Zhu J, Yamane H, Paul WE. Differentiation of effector CD4 T cell populations. Annu Rev Immunol 2010, 28:445-489. 10.1146/annurev-immunol-030409-101212, 20192806.
4. Nakayama T, Yamashita M. The TCR-mediated signaling pathways that control the direction of helper T cell differentiation. Semin Immunol 2010, 22:303-309. 10.1016/j.smim.2010.04.010, 20488727.
5. O'Shea JJ, Lahesmaa R, Vahedi G, Laurence A, Kanno Y. Genomic views of STAT function in CD4+ T helper cell differentiation. Nat Rev Immunol 2011, 11:239-250. 10.1038/nri2958, 3070307, 21436836.
6. Fang TC, Yashiro-Ohtani Y, Del Bianco C, Knoblock DM, Blacklow SC, Pear WS. Notch directly regulates Gata3 expression during T helper 2 cell differentiation. Immunity 2007, 27:100-110. 10.1016/j.immuni.2007.04.018, 2801546, 17658278.
7. Reynolds JM, Pappu BP, Peng J, Martinez GJ, Zhang Y, Chung Y, Ma L, Yang XO, Nurieva RI, Tian Q, Dong C. Toll-like receptor 2 signaling in CD4(+) T lymphocytes promotes T helper 17 responses and regulates the pathogenesis of autoimmune disease. Immunity 2010, 32:692-702. 10.1016/j.immuni.2010.04.010, 2878917, 20434372.
8. Amsen D, Blander JM, Lee GR, Tanigaki K, Honjo T, Flavell RA. Instruction of distinct CD4 T helper cell fates by different notch ligands on antigen-presenting cells. Cell 2004, 117:515-526.
9. Sher A, Coffman RL. Regulation of immunity to parasites by T cells and T cell-derived cytokines. Annu Rev Immunol 1992, 10:385-409. 10.1146/annurev.iy.10.040192.002125, 1590992.
10. O'Shea JJ, Paul WE. Mechanisms underlying lineage commitment and plasticity of helper CD4+ T cells. Science 2010, 327:1098-1102. 10.1126/science.1178334, 2997673, 20185720.
11. Murphy KM, Stockinger B. Effector T cell plasticity: flexibility in the face of changing circumstances. Nat Immunol 2010, 11:674-680. 3249647, 20644573.
12. Littman DR, Rudensky AY. Th17 and regulatory T cells in mediating and restraining inflammation. Cell 2010, 140:845-858. 10.1016/j.cell.2010.02.021, 20303875.
13. Romagnani S. Immunologic influences on allergy and the TH1/TH2 balance. J Allergy Clin Immunol 2004, 113:395-400. 10.1016/j.jaci.2003.11.025, 14758340.
14. Mauri C, Williams RO, Walmsley M, Feldmann M. Relationship between Th1/Th2 cytokine patterns and the arthritogenic response in collagen-induced arthritis. Eur J Immunol 1996, 26:1511-1518. 10.1002/eji.1830260716, 8766554.
15. Zhou L, Lopes JE, Chong MM, Ivanov II, Min R, Victora GD, Shen Y, Du J, Rubtsov YP, Rudensky AY, et al. TGF-beta-induced Foxp3 inhibits T(H)17 cell differentiation by antagonizing RORgammat function. Nature 2008, 453:236-240. 10.1038/nature06878, 2597437, 18368049.
16. Lochner M, Peduto L, Cherrier M, Sawa S, Langa F, Varona R, Riethmacher D, Si-Tahar M, Di Santo JP, Eberl G. In vivo equilibrium of proinflammatory IL-17+ and regulatory IL-10+ Foxp3+ RORgamma t + T cells. J Exp Med 2008, 205:1381-1393. 10.1084/jem.20080034, 2413035, 18504307.
17. Ghoreschi K, Laurence A, Yang XP, Tato CM, McGeachy MJ, Konkel JE, Ramos HL, Wei L, Davidson TS, Bouladoux N, et al. Generation of pathogenic T(H)17 cells in the absence of TGF-beta signalling. Nature 2010, 467:967-971. 10.1038/nature09447, 3108066, 20962846.
18. Yamashita M, Kimura M, Kubo M, Shimizu C, Tada T, Perlmutter RM, Nakayama T. 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 U S A 1999, 96:1024-1029. 10.1073/pnas.96.3.1024, 15344, 9927687.
19. Molinero LL, Miller ML, Evaristo C, Alegre ML. High TCR stimuli prevent induced regulatory T cell differentiation in a NF-kappaB-dependent manner. J Immunol 2011, 186:4609-4617. 10.4049/jimmunol.1002361, 21411734.
20. Hosken NA, Shibuya K, Heath AW, Murphy KM, O'Garra A. The effect of antigen dose on CD4+ T helper cell phenotype development in a T cell receptor-alpha beta-transgenic model. J Exp Med 1995, 182:1579-1584. 10.1084/jem.182.5.1579, 2192218, 7595228.
21. Messi M, Giacchetto I, Nagata K, Lanzavecchia A, Natoli G, Sallusto F. Memory and flexibility of cytokine gene expression as separable properties of human T(H)1 and T(H)2 lymphocytes. Nat Immunol 2003, 4:78-86. 10.1038/ni872, 12447360.
22. Ayyoub M, Deknuydt F, Raimbaud I, Dousset C, Leveque L, Bioley G, Valmori D. Human memory FOXP3+ Tregs secrete IL-17 ex vivo and constitutively express the T(H)17 lineage-specific transcription factor RORgamma t. Proc Natl Acad Sci U S A 2009, 106:8635-8640. 10.1073/pnas.0900621106, 2688993, 19439651.
23. Voo KS, Wang YH, Santori FR, Boggiano C, Arima K, Bover L, Hanabuchi S, Khalili J, Marinova E, Zheng B, et al. Identification of IL-17-producing FOXP3+ regulatory T cells in humans. Proc Natl Acad Sci U S A 2009, 106:4793-4798. 10.1073/pnas.0900408106, 2653560, 19273860.
24. Hegazy AN, Peine M, Helmstetter C, Panse I, Frohlich A, Bergthaler A, Flatz L, Pinschewer DD, Radbruch A, Lohning M. Interferons direct Th2 cell reprogramming to generate a stable GATA-3(+)T-bet(+) cell subset with combined Th2 and Th1 cell functions. Immunity 2010, 32:116-128. 10.1016/j.immuni.2009.12.004, 20079668.
25. Zhu J, Paul WE. Peripheral CD4+ T-cell differentiation regulated by networks of cytokines and transcription factors. Immunol Rev 2010, 238:247-262. 10.1111/j.1600-065X.2010.00951.x, 2975272, 20969597.
26. Abromson-Leeman S, Bronson RT, Dorf ME. Encephalitogenic T cells that stably express both T-bet and ROR gamma t consistently produce IFNgamma but have a spectrum of IL-17 profiles. J Neuroimmunol 2009, 215:10-24. 10.1016/j.jneuroim.2009.07.007, 2761534, 19692128.
27. Hofer T, Nathansen H, Lohning M, Radbruch A, Heinrich R. GATA-3 transcriptional imprinting in Th2 lymphocytes: a mathematical model. Proc Natl Acad Sci U S A 2002, 99:9364-9368. 10.1073/pnas.142284699, 123146, 12087127.
28. Mariani L, Lohning M, Radbruch A, Hofer T. Transcriptional control networks of cell differentiation: insights from helper T lymphocytes. Prog Biophys Mol Biol 2004, 86:45-76. 10.1016/j.pbiomolbio.2004.02.007, 15261525.
29. Yates A, Callard R, Stark J. Combining cytokine signalling with T-bet and GATA-3 regulation in Th1 and Th2 differentiation: a model for cellular decision-making. J Theor Biol 2004, 231:181-196. 10.1016/j.jtbi.2004.06.013, 15380383.
30. van den Ham HJ, de Boer RJ. From the two-dimensional Th1 and Th2 phenotypes to high-dimensional models for gene regulation. Int Immunol 2008, 20:1269-1277. 10.1093/intimm/dxn093, 18765426.
31. Mendoza L, Xenarios I. A method for the generation of standardized qualitative dynamical systems of regulatory networks. Theor Biol Med Model 2006, 3:13. 10.1186/1742-4682-3-13, 1440308, 16542429.
32. Naldi A, Carneiro J, Chaouiya C, Thieffry D. Diversity and plasticity of Th cell types predicted from regulatory network modelling. PLoS Comput Biol 2010, 6:e1000912. 10.1371/journal.pcbi.1000912, 2932677, 20824124.
33. Hong T, Xing J, Li L, Tyson JJ. A mathematical model for the reciprocal differentiation of T helper 17 cells and induced regulatory T cells. PLoS Comput Biol 2011, 7:e1002122. 10.1371/journal.pcbi.1002122, 3145653, 21829337.
34. Placek K, Gasparian S, Coffre M, Maiella S, Sechet E, Bianchi E, Rogge L. Integration of distinct intracellular signaling pathways at distal regulatory elements directs T-bet expression in human CD4+ T cells. J Immunol 2009, 183:7743-7751. 10.4049/jimmunol.0803812, 19923468.
35. Yamane H, Zhu J, Paul WE. Independent roles for IL-2 and GATA-3 in stimulating naive CD4+ T cells to generate a Th2-inducing cytokine environment. J Exp Med 2005, 202:793-804. 10.1084/jem.20051304, 2212937, 16172258.
36. Zhu J, Guo L, Watson CJ, Hu-Li J, Paul WE. Stat6 is necessary and sufficient for IL-4's role in Th2 differentiation and cell expansion. J Immunol 2001, 166:7276-7281.
37. Usui T, Preiss JC, Kanno Y, Yao ZJ, Bream JH, O'Shea JJ, Strober W. T-bet regulates Th1 responses through essential effects on GATA-3 function rather than on IFNG gene acetylation and transcription. J Exp Med 2006, 203:755-766. 10.1084/jem.20052165, 2118252, 16520391.
38. Zhu J, Jankovic D, Grinberg A, Guo L, Paul WE. Gfi-1 plays an important role in IL-2-mediated Th2 cell expansion. Proc Natl Acad Sci U S A 2006, 103:18214-18219. 10.1073/pnas.0608981103, 1654136, 17116877.
39. Mullen AC, High FA, Hutchins AS, Lee HW, Villarino AV, Livingston DM, Kung AL, Cereb N, Yao TP, Yang SY, Reiner SL. Role of T-bet in commitment of TH1 cells before IL-12-dependent selection. Science 2001, 292:1907-1910. 10.1126/science.1059835, 11397944.
40. Ouyang W, Lohning M, Gao Z, Assenmacher M, Ranganath S, Radbruch A, Murphy KM. Stat6-independent GATA-3 autoactivation directs IL-4-independent Th2 development and commitment. Immunity 2000, 12:27-37. 10.1016/S1074-7613(00)80156-9, 10661403.
41. Yang XO, Nurieva R, Martinez GJ, Kang HS, Chung Y, Pappu BP, Shah B, Chang SH, Schluns KS, Watowich SS, et al. Molecular antagonism and plasticity of regulatory and inflammatory T cell programs. Immunity 2008, 29:44-56. 10.1016/j.immuni.2008.05.007, 2630532, 18585065.
42. Yang L, Anderson DE, Baecher-Allan C, Hastings WD, Bettelli E, Oukka M, Kuchroo VK, Hafler DA. IL-21 and TGF-beta are required for differentiation of human T(H)17 cells. Nature 2008, 454:350-352. 10.1038/nature07021, 2760130, 18469800.
43. Gorelik L, Constant S, Flavell RA. Mechanism of transforming growth factor beta-induced inhibition of T helper type 1 differentiation. J Exp Med 2002, 195:1499-1505. 10.1084/jem.20012076, 2193549, 12045248.
44. Lazarevic V, Chen X, Shim JH, Hwang ES, Jang E, Bolm AN, Oukka M, Kuchroo VK, Glimcher LH. T-bet represses T(H)17 differentiation by preventing Runx1-mediated activation of the gene encoding RORgammat. Nat Immunol 2011, 12:96-104. 10.1038/ni.1969, 3077962, 21151104.
45. Mukasa R, Balasubramani A, Lee YK, Whitley SK, Weaver BT, Shibata Y, Crawford GE, Hatton RD, Weaver CT. Epigenetic instability of cytokine and transcription factor gene loci underlies plasticity of the T helper 17 cell lineage. Immunity 2010, 32:616-627. 10.1016/j.immuni.2010.04.016, 3129685, 20471290.
46. Gutcher I, Donkor MK, Ma Q, Rudensky AY, Flavell RA, Li MO. Autocrine transforming growth factor-beta1 promotes in vivo Th17 cell differentiation. Immunity 2011, 34:396-408. 10.1016/j.immuni.2011.03.005, 21435587.
47. Kimura A, Kishimoto T. IL-6: regulator of Treg/Th17 balance. Eur J Immunol 2010, 40:1830-1835. 10.1002/eji.201040391, 20583029.
48. Elias KM, Laurence A, Davidson TS, Stephens G, Kanno Y, Shevach EM, O'Shea JJ. Retinoic acid inhibits Th17 polarization and enhances FoxP3 expression through a Stat-3/Stat-5 independent signaling pathway. Blood 2008, 111:1013-1020. 2214761, 17951529.
49. Mucida D, Park Y, Kim G, Turovskaya O, Scott I, Kronenberg M, Cheroutre H. Reciprocal TH17 and regulatory T cell differentiation mediated by retinoic acid. Science 2007, 317:256-260. 10.1126/science.1145697, 17569825.
50. Gavin MA, Rasmussen JP, Fontenot JD, Vasta V, Manganiello VC, Beavo JA, Rudensky AY. Foxp3-dependent programme of regulatory T-cell differentiation. Nature 2007, 445:771-775. 10.1038/nature05543, 17220874.
51. Burgler S, Mantel PY, Bassin C, Ouaked N, Akdis CA, Schmidt-Weber CB. RORC2 is involved in T cell polarization through interaction with the FOXP3 promoter. J Immunol 2010, 184:6161-6169. 10.4049/jimmunol.0903243, 20427770.
52. Laslo P, Spooner CJ, Warmflash A, Lancki DW, Lee HJ, Sciammas R, Gantner BN, Dinner AR, Singh H. Multilineage transcriptional priming and determination of alternate hematopoietic cell fates. Cell 2006, 126:755-766. 10.1016/j.cell.2006.06.052, 16923394.
53. Huang S, Guo YP, May G, Enver T. Bifurcation dynamics in lineage-commitment in bipotent progenitor cells. Dev Biol 2007, 305:695-713. 10.1016/j.ydbio.2007.02.036, 17412320.
54. Guantes R, Poyatos JF. Multistable decision switches for flexible control of epigenetic differentiation. PLoS Comput Biol 2008, 4:e1000235. 10.1371/journal.pcbi.1000235, 2580821, 19043543.
55. Sciammas R, Li Y, Warmflash A, Song Y, Dinner AR, Singh H. An incoherent regulatory network architecture that orchestrates B cell diversification in response to antigen signaling. Mol Syst Biol 2011, 7:495. 3130558, 21613984.
56. Griffith JS. Mathematics of cellular control processes. II. Positive feedback to one gene. J Theor Biol 1968, 20:209-216. 10.1016/0022-5193(68)90190-2, 5727240.
57. Thomas R. Logical analysis of systems comprising feedback loops. J Theor Biol 1978, 73:631-656. 10.1016/0022-5193(78)90127-3, 703339.
58. Roessler OE. Basic circuits for fluid automata and relaxation systems. Z Naturforsch 1972, 27:333-343.
59. Maruyama T, Li J, Vaque JP, Konkel JE, Wang W, Zhang B, Zhang P, Zamarron BF, Yu D, Wu Y, et al. Control of the differentiation of regulatory T cells and T(H)17 cells by the DNA-binding inhibitor Id3. Nat Immunol 2011, 12:86-95. 10.1038/ni.1965, 3140164, 21131965.
60. Powell JD, Delgoffe GM. The mammalian target of rapamycin: linking T cell differentiation, function, and metabolism. Immunity 2010, 33:301-311. 10.1016/j.immuni.2010.09.002, 2962404, 20870173.
61. Stritesky GL, Muthukrishnan R, Sehra S, Goswami R, Pham D, Travers J, Nguyen ET, Levy DE, Kaplan MH. The transcription factor STAT3 is required for T helper 2 cell development. Immunity 2011, 34:39-49. 10.1016/j.immuni.2010.12.013, 3040244, 21215659.
62. Dong C. TH17 cells in development: an updated view of their molecular identity and genetic programming. Nat Rev Immunol 2008, 8:337-348. 10.1038/nri2295, 18408735.
63. Feinerman O, Veiga J, Dorfman JR, Germain RN, Altan-Bonnet G. Variability and robustness in T cell activation from regulated heterogeneity in protein levels. Science 2008, 321:1081-1084. 10.1126/science.1158013, 2673522, 18719282.
64. Chang HH, Hemberg M, Barahona M, Ingber DE, Huang S. Transcriptome-wide noise controls lineage choice in mammalian progenitor cells. Nature 2008, 453:544-547. 10.1038/nature06965, 18497826.
65. Wilson HR, Cowan JD. Excitatory and inhibitory interactions in localized populations of model neurons. Biophys J 1972, 12:1-24. 1484078, 4332108.
66. Mjolsness E, Sharp DH, Reinitz J. A connectionist model of development. J Theor Biol 1991, 152:429-453. 10.1016/S0022-5193(05)80391-1, 1758194.
67. Tyson JJ, Novak B. Functional motifs in biochemical reaction networks. Annu Rev Phys Chem 2010, 61:219-240. 10.1146/annurev.physchem.012809.103457, 20055671.
68. Clewley R, Sherwood WE, LaMar MD, Guckenheimer JM. PyDSTool, a software environment for dynamical systems modeling [http://pydstool.sourceforge.net].
69. Tyson JJ, Novak B. Temporal organization of the cell cycle. Curr Biol 2008, 18:R759-R768. 10.1016/j.cub.2008.07.001, 2856080, 18786381.