白细胞介素-35在自身免疫性疾病中的研究进展_《华西医学》

作者：

李芳 ^1,2 , 吴永强 ³ ,  石桂秀 ¹

四川大学（成都，610041） 1华西医院风湿免疫科， 2华西临床医学院，3华西医院再生医学研究中心;

关键词：

IL-35 调节性T细胞自身免疫

DOI：

10.7507/1002-0179.20130298

视频：

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摘要 全文 图表 视频 参考文献 施引文献 补充材料

白细胞介素（IL）-35是IL-12家族中新的一员，由EB病毒诱导基因3产物（Ebi3）和IL-12p35亚基形成的异二聚体，它可由调节性T（Treg）细胞特异性产生，是Treg细胞介导的免疫调节作用所必需的细胞因子。增加IL-35可抑制一些自身免疫性疾病如动物模型中的CIA等，证明了它在炎性细胞因子介导的疾病中存有潜在的治疗作用。但是，很多和IL-35相关的问题仍然不清楚，比如IL-35的受体结构、介导的细胞信号通路、以及在人细胞中的表达模式。虽然IL-35与IL-12家族中的IL-12和IL-27有共同亚基，然而IL-35有着不同的生物学功能，因此拟通过对既往有关IL-12家族的许多室验结论进行再评价，以期望探索IL-35在其中所起到的作用。

引用本文： 李芳,吴永强,石桂秀. 白细胞介素-35在自身免疫性疾病中的研究进展. 华西医学, 2013, 28(6): 948-954. doi: 10.7507/1002-0179.20130298 复制

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1. 　Stern AS, Podlaski FJ, Hulmes JD, et al. Purification to homogeneity and partial characterization of cytotoxic lymphocyte maturation factor from human B-lymphoblastoid cells[J]. Proceedings of the National Academy of Sciences of the United States of America, 1990, 87(17): 6808-6812.
2. 　Schoenhaut DS, Chua AO, Wolitzky AG, et al. Cloning and expression of murine IL-12[J]. J Immunol, 1992, 148(11): 3433-3440.
3. 　Oppmann B, Lesley R, Blom B, et al. Novel p19 protein engages IL-12p40 to form a cytokine, IL-23, with biological activities similar as well as distinct from IL-12[J]. Immunity, 2000, 13(5): 715-725.
4. 　Pflanz S, Timans JC, Cheung J, et al. IL-27, a heterodimeric cytokine composed of EBI3 and p28 protein, induces proliferation of naive CD4(+) T cells[J]. Immunity, 2002, 16(6): 779-790.
5. 　Devergne O, Hummel M, Koeppen H, et al. A novel interleukin-12 p40-related protein induced by latent Epstein-Barr virus infection in B lymphocytes[J]. Journal of virology, 1996, 70(2): 1143-1153.
6. 　Gehlert T, Devergne O, Niedobitek G. Epstein-Barr virus (EBV) infection and expression of the interleukin-12 family member EBV-induced gene 3 (EBI3) in chronic inflammatory bowel disease[J]. Journal of medical virology, 2004, 73(3): 432-438.
7. 　Trinchieri G. Interleukin-12 and the regulation of innate resistance and adaptive immunity[J]. Nature reviews Immunology, 2003, 3(2): 133-146.
8. 　Nagai H, Oniki S, Fujiwara S, et al. Antitumor activities of interleukin-27 on melanoma[J]. Endocrine, metabolic & immune disorders drug targets, 2010, 10(1): 41-46.
9. 　Goriely S, Goldman M. The interleukin-12 family: new players in transplantation immunity[J]? American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons, 2007, 7(2): 278-284.
10. 　Wang KS, Frank DA, Ritz J. Interleukin-2 enhances the response of natural killer cells to interleukin-12 through up-regulation of the interleukin-12 receptor and STAT4[J]. Blood, 2000, 95(10): 3183-3190.
11. 　van de Vosse E, Lichtenauer-Kaligis EG, van Dissel JT, et al. Genetic variations in the interleukin-12/interleukin-23 receptor (beta1) chain, and implications for IL-12 and IL-23 receptor structure and function[J]. Immunogenetics, 2003, 54(12): 817-829.
12. 　Parham C, Chirica M, Timans J, et al. A receptor for the heterodimeric cytokine IL-23 is composed of IL-12Rbeta1 and a novel cytokine receptor subunit, IL-23R[J]. J Immunol, 2002, 168(11): 5699-5708.
13. 　Pflanz S, Hibbert L, Mattson J, et al. WSX-1 and glycoprotein 130 constitute a signal-transducing receptor for IL-27[J]. J Immunol, 2004, 172(4): 2225-2231.
14. 　Taga T, Kishimoto T. Gp130 and the interleukin-6 family of cytokines[J]. Annual review of immunology, 1997, 15: 797-819.
15. 　Ihle JN, Witthuhn BA, Quelle FW, et al. Signaling through the hematopoietic cytokine receptors[J]. Annual review of immunology, 1995, 13: 369-398.
16. 　Heinrich PC, Behrmann I, Muller-Newen G, et al. Interleukin-6-type cytokine signalling through the gp130/Jak/STAT pathway[J]. The Biochemical journal, 1998, 334 ( Pt 2): 297-314.
17. 　Ning-Wei Z. Interleukin (IL)-35 is raising our expectations[J]. Revista medica de Chile, 2010, 138(6): 758-766.
18. 　Collison LW, Vignali DA. Interleukin-35: odd one out or part of the family? [J] Immunological reviews, 2008, 226: 248-262.
19. 　Takaoka A, Yanai H, Kondo S, et al. Integral role of IRF-5 in the gene induction programme activated by Toll-like receptors[J]. Nature, 2005, 434(7030): 243-249.
20. 　Ouyang X, Negishi H, Takeda R, et al. Cooperation between MyD88 and TRIF pathways in TLR synergy via IRF5 activation[J]. Biochemical and biophysical research communications, 2007, 354(4): 1045-1051.
21. 　Negishi H, Fujita Y, Yanai H, et al. Evidence for licensing of IFN-gamma-induced IFN regulatory factor 1 transcription factor by MyD88 in Toll-like receptor-dependent gene induction program[J]. Proceedings of the National Academy of Sciences of the United States of America, 2006, 103(41): 15136-15141.
22. 　Goriely S, Molle C, Nguyen M, et al. Interferon regulatory factor 3 is involved in Toll-like receptor 4 (TLR4)- and TLR3-induced IL-12p35 gene activation[J]. Blood, 2006, 107(3): 1078-1084.
23. 　Liu J, Cao S, Herman LM, et al. Differential regulation of interleukin (IL)-12 p35 and p40 gene expression and interferon (IFN)-gamma-primed IL-12 production by IFN regulatory factor 1[J]. The Journal of experimental medicine, 2003, 198(8): 1265-1276.
24. 　Liu J, Guan X, Tamura T, et al. Synergistic activation of interleukin-12 p35 gene transcription by interferon regulatory factor-1 and interferon consensus sequence-binding protein[J]. The Journal of biological chemistry, 2004, 279(53): 55609-55617.
25. 　Weinmann AS, Plevy SE, Smale ST. Rapid and selective remodeling of a positioned nucleosome during the induction of IL-12 p40 transcription[J]. Immunity, 1999, 11(6): 665-675.
26. 　Goriely S, Demonte D, Nizet S, et al. Human IL-12(p35) gene activation involves selective remodeling of a single nucleosome within a region of the promoter containing critical Sp1-binding sites[J]. Blood, 2003, 101(12): 4894-4902.
27. 　Goriely S, Neurath MF, Goldman M. How microorganisms tip the balance between interleukin-12 family members[J]. Nature reviews Immunology, 2008, 8(1): 81-86.
28. 　Wirtz S, Becker C, Fantini MC, et al. EBV-induced gene 3 transcription is induced by TLR signaling in primary dendritic cells via NF-kappa B activation[J]. J Immunol, 2005, 174(5): 2814-2824.
29. 　Fantini MC, Becker C, Monteleone G, et al. Cutting edge: TGF-beta induces a regulatory phenotype in CD4+CD25- T cells through Foxp3 induction and down-regulation of Smad7[J]. J Immunol, 2004, 172(9): 5149-5153.
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