Activated IL-23/IL-17 pathway closely correlates with increased Foxp3 expression in livers of chronic hepatitis B patients

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• 作者：Qinghong Wang (1) (2)
  Yanhua Zheng (2)
  Zemin Huang (2)
  Yi Tian (2)
  Jijun Zhou (3)
  Qing Mao (3)
  Yuzhang Wu (2)
  Bing Ni (2)
  
• 关键词：Treg ; Foxp3 ; Th17 ; IL ; 23 ; IL ; 17 ; Hepatitis B
• 刊名：BMC Immunology
• 出版年：2011
• 出版时间：December 2011
• 年：2011
• 卷：12
• 期：1
• 全文大小：3442KB
• 参考文献：1. Rehermann B, Nascimbeni M: Immunology of hepatitis B virus and hepatitis C virus infection. / Nat Rev Immunol 2005, 5:215鈥?9. CrossRef
  2. Lohse AW, Weiler-Normann C, Tiegs G: Immune-mediated liver injury. / J Hepatol 2010, 52:136鈥?4. CrossRef
  3. Webster GJ, Reignat S, Brown D, Ogg GS, Jones L, Seneviratne SL, Williams R, Dusheiko G, Bertoletti A: Longitudinal analysis of CD8+ T cells specific for structural and nonstructural hepatitis B virus proteins in patients with chronic hepatitis B: implications for immunotherapy. / J Virol 2004, 78:5707鈥?9. CrossRef
  4. Roncador G, Brown PJ, Maestre L, Hue S, Martinez-Torrecuadrada JL, Ling KL, Pratap S, Toms C, Fox BC, Cerundolo V, Powrie F, Banham AH: Analysis of FOXP3 protein expression in human CD4+CD25+ regulatory T cells at the single-cell level. / Eur J Immunol 2005, 35:1681鈥?1. CrossRef
  5. Hirota K, Yoshitomi H, Tanaka S, Nomura T, Yamaguchi T, Iwakura Y, Sakaguchi N, Sakaguchi S: T cell self-reactivity forms a cytokine milieu for spontaneous development of IL-17+ Th cells that cause autoimmune arthritis. / J Exp Med 2007, 204:41鈥?. CrossRef
  6. Leifeld L, Cheng S, Ramakers J, Dumoulin FL, Trautwein C, Sauerbruch T, Spengler U: Imbalanced intrahepatic expression of interleukin 12, interferon gamma, and interleukin 10 in fulminant hepatitis B. / Hepatology 2002, 36:1001鈥?.
  7. Stoop JN, Claassen MA, Woltman AM, Binda RS, Kuipers EJ, Janssen HL, van der Molen RG, Boonstra A: Intrahepatic regulatory T cells are phenotypically distinct from their peripheral counterparts in chronic HBV patients. / Clin Immunol 2008, 129:419鈥?7. CrossRef
  8. Stoop JN, van der Molen RG, Baan CC, van der Laan LJ, Kuipers EJ, Kusters JG, Janssen HL: Regulatory T cells contribute to the impaired immune response in patients with chronic hepatitis B virus infection. / Hepatology 2005, 41:771鈥?. CrossRef
  9. Xu D, Fu J, Jin L, Zhang H, Zhou C, Zou Z, Zhao JM, Zhang B, Shi M, Ding X, Tang Z, Fu YX, Wang FS: Circulating and liver resident CD4+CD25+ regulatory T cells actively influence the antiviral immune response and disease progression in patients with hepatitis B. / J Immunol 2006, 177:739鈥?7.
  10. Kleinschek MA, Owyang AM, Joyce-Shaikh B, Langrish CL, Chen Y, Gorman DM, Blumenschein WM, McClanahan T, Brombacher F, Hurst SD, Kastelein RA, Cua DJ: IL-25 regulates Th17 function in autoimmune inflammation. / J Exp Med 2007, 204:161鈥?0. CrossRef
  11. Sallusto F, Lanzavecchia A: Human Th17 cells in infection and autoimmunity. / Microbes Infect 2009, 11:620鈥?. CrossRef
  12. Romagnani S, Maggi E, Liotta F, Cosmi L, Annunziato F: Properties and origin of human Th17 cells. / Mol Immunol 2009, 47:3鈥?. CrossRef
  13. Ge J, Wang K, Meng QH, Qi ZX, Meng FL, Fan YC: Implication of Th17 and Th1 cells in patients with chronic active hepatitis B. / J Clin Immunol 2010, 30:60鈥?. CrossRef
  14. Zhang JY, Zhang Z, Lin F, Zou ZS, Xu RN, Jin L, Fu JL, Shi F, Shi M, Wang HF, Wang FS: Interleukin-17-producing CD4(+) T cells increase with severity of liver damage in patients with chronic hepatitis B. / Hepatology 2010, 51:81鈥?1.
  15. Zhang Z, Chen D, Yao J, Zhang H, Jin L, Shi M, Zhang H, Wang FS: Increased infiltration of intrahepatic DC subsets closely correlate with viral control and liver injury in immune active pediatric patients with chronic hepatitis B. / Clin Immunol 2007, 122:173鈥?0. CrossRef
  16. O'Connor RA, Taams LS, Anderton SM: Translational mini-review series on Th17 cells: CD4 T helper cells: functional plasticity and differential sensitivity to regulatory T cell-mediated regulation. / Clin Exp Immunol 2010, 159:137鈥?7. CrossRef
  17. Miossec P: IL-17 and Th17 cells in human inflammatory diseases. / Microbes Infect 2009, 11:625鈥?0. CrossRef
  18. Duerr RH, Taylor KD, Brant SR, Rioux JD, Silverberg MS, Daly MJ, Steinhart AH, Abraham C, Regueiro M, Griffiths A, Dassopoulos T, Bitton A, Yang H, Targan S, Datta LW, Kistner EO, Schumm LP, Lee AT, Gregersen PK, Barmada MM, Rotter JI, Nicolae DL, Cho JH: A genome-wide association study identifies IL23R as an inflammatory bowel disease gene. / Science 2006, 314:1461鈥?. CrossRef
  19. Weaver CT, Hatton RD: Interplay between the TH17 and TReg cell lineages: a (co-)evolutionary perspective. / Nat Rev Immunol 2009, 9:883鈥?. CrossRef
  20. Nistala K, Moncrieffe H, Newton KR, Varsani H, Hunter P, Wedderburn LR: Interleukin-17-producing T cells are enriched in the joints of children with arthritis, but have a reciprocal relationship to regulatory T cell numbers. / Arthritis Rheum 2008, 58:875鈥?7. CrossRef
  21. Manigold T, Racanelli V: T-cell regulation by CD4 regulatory T cells during hepatitis B and C virus infections: facts and controversies. / Lancet Infect Dis 2007, 7:804鈥?3. CrossRef
  22. Gupta S: Immune homeostasis: regulatory T cells (Treg) and molecules. / J Clin Immunol 2008, 28:617鈥?. CrossRef
  23. Pernis AB: Th17 cells in rheumatoid arthritis and systemic lupus erythematosus. / J Intern Med 2009, 265:644鈥?2. CrossRef
  24. Di Cesare A, Di Meglio P, Nestle FO: The IL-23/Th17 axis in the immunopathogenesis of psoriasis. / J Invest Dermatol 2009, 129:1339鈥?0. CrossRef
  25. Annunziato F, Cosmi L, Santarlasci V, Maggi L, Liotta F, Mazzinghi B, Parente E, Fili L, Ferri S, Frosali F, Giudici F, Romagnani P, Parronchi P, Tonelli F, Maggi E, Romagnani S: Phenotypic and functional features of human Th17 cells. / J Exp Med 2007, 204:1849鈥?1. CrossRef
  26. Lemmers A, Moreno C, Gustot T, Marechal R, Degre D, Demetter P, de Nadai P, Geerts A, Quertinmont E, Vercruysse V, Le Moine O, Devi猫re J: The interleukin-17 pathway is involved in human alcoholic liver disease. / Hepatology 2009, 49:646鈥?7. CrossRef
  27. Kuang DM, Peng C, Zhao Q, Wu Y, Chen MS, Zheng L: Activated monocytes in peritumoral stroma of hepatocellular carcinoma promote expansion of memory T helper 17 cells. / Hepatology 2010, 51:154鈥?4.
  28. Lee JH, Cho ML, Kim JI, Moon YM, Oh HJ, Kim GT, Ryu S, Baek SH, Lee SH, Kim HY, Kim SI: Interleukin 17 (IL-17) increases the expression of Toll-like receptor-2, 4, and 9 by increasing IL-1beta and IL-6 production in autoimmune arthritis. / J Rheumatol 2009, 36:684鈥?2. CrossRef
  29. Martin-Orozco N, Muranski P, Chung Y, Yang XO, Yamazaki T, Lu S, Hwu P, Restifo NP, Overwijk WW, Dong C: T Helper 17 Cells Promote Cytotoxic T Cell Activation in Tumor Immunity. / Immunity 2009, 31:787鈥?8. CrossRef
  30. Li N, Bian H, Zhang J, Li X, Ji X, Zhang Y: The Th17/Treg imbalance exists in patients with heart failure with normal ejection fraction and heart failure with reduced ejection fraction. / Clin Chim Acta 2010, 411:1963鈥?. CrossRef
  31. Li J, Wang L, Wang S, Zhu H, Ye P, Xie A, Shen B, Liu C, Guo C, Fu Q, Zhang K, Xia J: The Treg/Th17 imbalance in patients with idiopathic dilated cardiomyopathy. / Scand J Immunol 2010, 71:298鈥?03. CrossRef
  32. Korn T, Bettelli E, Oukka M, Kuchroo VK: IL-17 and Th17 Cells. / Annu Rev Immuno 2009, 27:485鈥?17. CrossRef
  33. 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鈥?0. CrossRef
  34. Laurence A, Tato CM, Davidson TS, Kanno Y, Chen Z, Yao Z, Blank RB, Meylan F, Siegel R, Hennighausen L, Shevach EM, O'shea JJ: Interleukin-2 signaling via STAT5 constrains T helper 17 cell generation. / Immunity 2007, 26:371鈥?1. CrossRef
  35. Kryczek I, Wei S, Zou L, Altuwaijri S, Szeliga W, Kolls J, Chang A, Zou W: Cutting edge: Th17 and regulatory T cell dynamics and the regulation by IL-2 in the tumor microenvironment. / J Immunol 2007, 178:6730鈥?.
  36. Pyzik M, Piccirillo CA: TGF-beta1 modulates Foxp3 expression and regulatory activity in distinct CD4+ T cell subsets. / J Leukoc Biol 2007, 82:335鈥?6. CrossRef
  37. Manel N, Unutmaz D, Littman DR: The differentiation of human T(H)-17 cells requires transforming growth factor-beta and induction of the nuclear receptor RORgammat. / Nat Immunol 2008, 9:641鈥?. CrossRef
  38. Voo KS, Wang YH, Santori FR, Boggiano C, Wang YH, Arima K, Bover L, Hanabuchi S, Khalili J, Marinova E, Zheng B, Littman DR, Liu YJ: Identification of IL-17-producing FOXP3+ regulatory T cells in humans. / Proc Natl Acad Sci USA 2009, 106:4793鈥?. CrossRef
  39. 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 USA 2009, 106:8635鈥?0. CrossRef
  40. Zhang L, Yang XQ, Cheng J, Hui RS, Gao TW: Increased Th17 cells are accompanied by FoxP3(+) Treg cell accumulation and correlated with psoriasis disease severity. / Clin Immunol 2010, 135:108鈥?7. CrossRef
  
• 作者单位：Qinghong Wang (1) (2)
  Yanhua Zheng (2)
  Zemin Huang (2)
  Yi Tian (2)
  Jijun Zhou (3)
  Qing Mao (3)
  Yuzhang Wu (2)
  Bing Ni (2)
  
  1. Ministry of Education Key Laboratory of Child Development and Disorders, Pediatric Research Institute, Children鈥檚 Hospital of Chongqing Medical University, Chongqing, 400014, PR China
  2. Institute of Immunology, PLA, Third Military Medical University, Chongqing, 400038, PR China
  3. Department of Infectious Diseases, Southwestern Hospital, Third Military Medical University, Chongqing, 400038, PR China
  
• ISSN：1471-2172

文摘

Background Foxp3 protein plays a critical role in mediating the inflammatory response and can inhibit the proinflammatory IL-23/IL-17 pathway. However, the molecular interplay of Foxp3 and the IL-23/IL-17 pathway in patients with chronic hepatitis B (CHB) remains unclear. To this end, we analyzed the expression patterns of Foxp3- and IL-23/IL-17 pathway-related proinflammatory cytokines in 39 patients with acute-on-chronic liver failure, 71 patients with CHB and 32 healthy controls. Results Foxp3 expression was found to be elevated in and mainly expressed by the CD4+ T cell sub-population of peripheral blood mononuclear cells and liver tissues of patients with hepatitis B. The intrahepatic expression of Foxp3 strongly correlated with the copies of HBV DNA and the concentration of surface antigen, HBsAg. IL-23/IL-17 pathway-related proinflammatory cytokines were also found to be significantly increased in patients' liver tissues, as compared to healthy controls. Moreover, Foxp3 expression was strikingly correlated with the production of these cytokines in liver tissues of CHB patients. Conclusions The closely-correlated increase of Foxp3 and IL-23/IL-17 pathway activity in HBV-infected livers suggests that the proinflammatory IL-23/IL-17 pathway had not been effectively suppressed by the host immune machinery, such as Treg (Foxp3) cells. Constitutive activation of the IL-23/17 pathway, thus, may support the chronic hepatitis B state.