白細胞介素-35在自身免疫性疾病中的研究進展_《華西醫學》

作者：

李芳 ^1,2 , 吳永強 ³ ,  石桂秀 ¹

四川大學（成都，610041） 1華西醫院風濕免疫科， 2華西臨床醫學院，3華西醫院再生醫學研究中心;

關鍵詞：

IL-35 調節性T細胞自身免疫

DOI：

10.7507/1002-0179.20130298

視頻：

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摘要 全文 圖表 視頻 參考文獻 施引文獻 補充材料

白細胞介素（IL）-35是IL-12家族中新的一員，由EB病毒誘導基因3產物（Ebi3）和IL-12p35亞基形成的異二聚體，它可由調節性T（Treg）細胞特異性產生，是Treg細胞介導的免疫調節作用所必需的細胞因子。增加IL-35可抑制一些自身免疫性疾病如動物模型中的CIA等，證明了它在炎性細胞因子介導的疾病中存有潛在的治療作用。但是，很多和IL-35相關的問題仍然不清楚，比如IL-35的受體結構、介導的細胞信號通路、以及在人細胞中的表達模式。雖然IL-35與IL-12家族中的IL-12和IL-27有共同亞基，然而IL-35有著不同的生物學功能，因此擬通過對既往有關IL-12家族的許多室驗結論進行再評價，以期望探索IL-35在其中所起到的作用。

引用本文： 李芳,吳永強,石桂秀. 白細胞介素-35在自身免疫性疾病中的研究進展. 華西醫學, 2013, 28(6): 948-954. doi: 10.7507/1002-0179.20130298 復制

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.
30.	Zheng SG, Wang JH, Koss MN, et al. CD4+ and CD8+ regulatory T cells generated ex vivo with IL-2 and TGF-beta suppress a stimulatory graft-versus-host disease with a lupus-like syndrome[J]. J Immunol, 2004, 172(3): 1531-1539.
31.	Tran DQ, Ramsey H, Shevach EM. Induction of FOXP3 expression in naive human CD4+FOXP3 T cells by T-cell receptor stimulation is transforming growth factor-beta dependent but does not confer a regulatory phenotype[J]. Blood, 2007, 110(8): 2983-2990.
32.	Collison LW, Workman CJ, Kuo TT, et al. The inhibitory cytokine IL-35 contributes to regulatory T-cell function[J]. Nature, 2007, 450(7169): 566-569.
33.	Zheng Y, Josefowicz SZ, Kas A, et al. Genome-wide analysis of Foxp3 target genes in developing and mature regulatory T cells[J]. Nature, 2007, 445(7130): 936-940.
34.	Wolf SF, Temple PA, Kobayashi M, et al. Cloning of cDNA for natural killer cell stimulatory factor, a heterodimeric cytokine with multiple biologic effects on T and natural killer cells[J]. J Immunol, 1991, 146(9): 3074-3081.
35.	Allan SE, Song-Zhao GX, Abraham T, et al. Inducible reprogramming of human T cells into Treg cells by a conditionally active form of FOXP3[J]. European journal of immunology, 2008, 38(12): 3282-3289.
36.	Chaturvedi V, Collison LW, Guy CS, et al. Cutting edge: Human regulatory T cells require IL-35 to mediate suppression and infectious tolerance[J]. J Immunol, 2011, 186(12): 6661-6666.
37.	Morgan ME, Flierman R, van Duivenvoorde LM, et al. Effective treatment of collagen-induced arthritis by adoptive transfer of CD25+ regulatory T cells[J]. Arthritis and rheumatism, 2005, 52(7): 2212-2221.
38.	Morgan ME, Sutmuller RP, Witteveen HJ, et al. CD25+ cell depletion hastens the onset of severe disease in collagen-induced arthritis[J]. Arthritis and rheumatism, 2003, 48(5): 1452-1460.
39.	Gonzalez-Rey E, Fernandez-Martin A, Chorny A, et al. Vasoactive intestinal peptide induces CD4+,CD25+ T regulatory cells with therapeutic effect in collagen-induced arthritis[J]. Arthritis and rheumatism, 2006, 54(3): 864-876.
40.	Niedbala W, Wei XQ, Cai B, et al. IL-35 is a novel cytokine with therapeutic effects against collagen-induced arthritis through the expansion of regulatory T cells and suppression of Th17 cells[J]. European journal of immunology, 2007, 37(11): 3021-3029.
41.	Schottelius AJ, Mayo MW, Sartor RB, et al. Interleukin-10 signaling blocks inhibitor of kappaB kinase activity and nuclear factor kappaB DNA binding[J]. The Journal of biological chemistry, 1999, 274(45): 31868-31874.
42.	Collison LW, Pillai MR, Chaturvedi V, et al. Regulatory T cell suppression is potentiated by target T cells in a cell contact, IL-35- and IL-10-dependent manner[J]. J Immunol, 2009, 182(10): 6121-6128.
43.	Mottet C, Uhlig HH, Powrie F. Cutting edge: cure of colitis by CD4+CD25+ regulatory T cells[J]. J Immunol, 2003, 170(8): 3939-3943.
44.	Colgan J, Rothman P. All in the family: IL-27 suppression of T(H)-17 cells[J]. Nature immunology, 2006, 7(9): 899-901.
45.	Niedbala W, Cai B, Liu H, et al. Nitric oxide induces CD4+CD25+ Foxp3 regulatory T cells from CD4+CD25 T cells via p53, IL-2, and OX40[J]. Proceedings of the National Academy of Sciences of the United States of America, 2007, 104(39): 15478-15483.
46.	Lund JM, Hsing L, Pham TT, et al. Coordination of early protective immunity to viral infection by regulatory T cells[J]. Science, 2008, 320(5880): 1220-1224.
47.	Haribhai D, Lin W, Relland LM, et al. Regulatory T cells dynamically control the primary immune response to foreign antigen[J]. J Immunol, 2007, 178(5): 2961-2972.
48.	Kim JM, Rasmussen JP, Rudensky AY. Regulatory T cells prevent catastrophic autoimmunity throughout the lifespan of mice[J]. Nature immunology, 2007, 8(2): 191-197.
49.	Kassiotis G, O’Garra A. Immunology. Immunity benefits from a little suppression[J]. Science, 2008, 320(5880): 1168-1169.
50.	Kempe S, Heinz P, Kokai E, et al. Epstein-barr virus-induced gene-3 is expressed in human atheroma plaques[J]. The American journal of pathology, 2009, 175(1): 440-447.
51.	Hsieh CS, Liang Y, Tyznik AJ, et al. Recognition of the peripheral self by naturally arising CD25+ CD4+ T cell receptors[J]. Immunity, 2004, 21(2): 267-277.
52.	Pacholczyk R, Ignatowicz H, Kraj P, et al. Origin and T cell receptor diversity of Foxp3+CD4+CD25+ T cells[J]. Immunity, 2006, 25(2): 249-259.
53.	Almeida AR, Zaragoza B, Freitas AA. Indexation as a novel mechanism of lymphocyte homeostasis: the number of CD4+CD25+ regulatory T cells is indexed to the number of IL-2-producing cells[J]. J Immunol, 2006, 177(1): 192-200.
54.	Bettelli E, Carrier Y, Gao W, et al. Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells[J]. Nature, 200, 441(7090): 235-238.
55.	Harrington LE, Hatton RD, Mangan PR, et al. Interleukin 17-producing CD4+ effector T cells develop via a lineage distinct from the T helper type 1 and 2 lineages[J]. Nature immunology, 2005, 6(11): 1123-1132.
56.	Wahl SM, Wen J, Moutsopoulos N. TGF-beta: a mobile purveyor of immune privilege[J]. Immunological reviews, 2006, 213: 213-227.
57.	Park H, Li Z, Yang XO, et al. A distinct lineage of CD4 T cells regulates tissue inflammation by producing interleukin 17[J]. Nature immunology, 2005, 6(11): 1133-1141.
58.	Kolls JK, Linden A. Interleukin-17 family members and inflammation[J]. Immunity, 2004, 21(4): 467-476.
59.	Langrish CL, Chen Y, Blumenschein WM, et al. IL-23 drives a pathogenic T cell population that induces autoimmune inflammation[J]. The Journal of experimental medicine, 2005, 201(2): 233-240.
60.	Ivanov, II, McKenzie BS, Zhou L, et al. The orphan nuclear receptor RORgammat directs the differentiation program of proinflammatory IL-17+ T helper cells[J]. Cell, 2006, 126(6): 1121-1133.
61.	Yang J, Yang M, Htut TM, et al. Epstein-Barr virus-induced gene 3 negatively regulates IL-17, IL-22 and RORgamma t[J]. European journal of immunology, 2008, 38(5): 1204-1214.
62.	Steinman L. Multiple sclerosis: a coordinated immunological attack against myelin in the central nervous system[J]. Cell, 1996, 85(3): 299-302.
63.	Zheng Y, Rudensky AY. Foxp3 in control of the regulatory T cell lineage[J]. Nature immunology, 2007, 8(5): 457-462.
64.	Adorini L. Interleukin-12, a key cytokine in Th1-mediated autoimmune diseases[J]. Cellular and molecular life sciences : CMLS, 1999, 55(12): 1610-1625.
65.	Karp CL, Biron CA, Irani DN. Interferon beta in multiple sclerosis: is IL-12 suppression the key? [J]Immunology today, 2000, 21(1): 24-28.
66.	Constantinescu CS, Wysocka M, Hilliard B, et al. Antibodies against IL-12 prevent superantigen-induced and spontaneous relapses of experimental autoimmune encephalomyelitis[J]. J Immunol, 1998, 161(9): 5097-5104.
67.	Leonard JP, Waldburger KE, Goldman SJ. Prevention of experimental autoimmune encephalomyelitis by antibodies against interleukin 12[J]. The Journal of experimental medicine, 1995, 181(1): 381-386.
68.	Costa GL, Sandora MR, Nakajima A, et al. Adoptive immunotherapy of experimental autoimmune encephalomyelitis via T cell delivery of the IL-12 p40 subunit[J]. J Immunol, 2001, 167(4): 2379-2387.
69.	Becher B, Durell BG, Noelle RJ. Experimental autoimmune encephalitis and inflammation in the absence of interleukin-12[J]. The Journal of clinical investigation, 2002, 110(4): 493-497.
70.	Gran B, Zhang GX, Yu S, et al. IL-12p35-deficient mice are susceptible to experimental autoimmune encephalomyelitis: evidence for redundancy in the IL-12 system in the induction of central nervous system autoimmune demyelination[J]. J Immunol, 2002, 169(12): 7104-7110.
71.	Cua DJ, Sherlock J, Chen Y, et al. Interleukin-23 rather than interleukin-12 is the critical cytokine for autoimmune inflammation of the brain[J]. Nature, 2003, 421(6924): 744-748.
72.	Aggarwal S, Ghilardi N, Xie MH, et al. Interleukin-23 promotes a distinct CD4 T cell activation state characterized by the production of interleukin-17[J]. The Journal of biological chemistry, 2003, 278(3): 1910-1914.
73.	Nagai T, Devergne O, van Seventer GA, et al. Interferon-beta mediates opposing effects on interferon-gamma-dependent Interleukin-12 p70 secretion by human monocyte-derived dendritic cells[J]. Scandinavian journal of immunology, 2007, 65(2): 107-117.
74.	Goldberg R, Zohar Y, Wildbaum G, et al. Suppression of ongoing experimental autoimmune encephalomyelitis by neutralizing the function of the p28 subunit of IL-27[J]. J Immunol, 2004, 173(10): 6465-6471.
75.	Kohm AP, Carpentier PA, Anger HA, et al. Cutting edge: CD4+CD25+ regulatory T cells suppress antigen-specific autoreactive immune responses and central nervous system inflammation during active experimental autoimmune encephalomyelitis[J]. J Immunol, 2002, 169(9): 4712-4716.
76.	McHugh RS, Shevach EM. The role of suppressor T cells in regulation of immune responses[J]. The Journal of allergy and clinical immunology, 2002, 110(5): 693-702.
77.	McGeachy MJ, Stephens LA, Anderton SM. Natural recovery and protection from autoimmune encephalomyelitis: contribution of CD4+CD25+ regulatory cells within the central nervous system[J]. J Immunol, 2005, 175(5): 3025-3032.
78.	Neu N, Rose NR, Beisel KW, et al. Cardiac myosin induces myocarditis in genetically predisposed mice[J]. J Immunol, 1987, 139(11): 3630-3636.
79.	Reddy J, Illes Z, Zhang X, et al. Myelin proteolipid protein-specific CD4+CD25+ regulatory cells mediate genetic resistance to experimental autoimmune encephalomyelitis[J]. Proceedings of the National Academy of Sciences of the United States of America, 2004, 101(43): 15434-15439.
80.	Thakker P, Leach MW, Kuang W, et al. IL-23 is critical in the induction but not in the effector phase of experimental autoimmune encephalomyelitis[J]. J Immunol, 2007, 178(4): 2589-2598.
81.	Courtenay JS, Dallman MJ, Dayan AD, et al. Immunisation against heterologous type II collagen induces arthritis in mice[J]. Nature, 1980, 283(5748): 666-668.
82.	Lubberts E, van den Bersselaar L, Oppers-Walgreen B, et al. IL-17 promotes bone erosion in murine collagen-induced arthritis through loss of the receptor activator of NF-kappa B ligand/osteoprotegerin balance[J]. J Immunol, 2003, 170(5): 2655-2662.
83.	Rohn TA, Jennings GT, Hernandez M, et al. Vaccination against IL-17 suppresses autoimmune arthritis and encephalomyelitis[J]. European journal of immunology, 2006, 36(11): 2857-2867.
84.	Murphy CA, Langrish CL, Chen Y, et al. Divergent pro- and antiinflammatory roles for IL-23 and IL-12 in joint autoimmune inflammation[J]. The Journal of experimental medicine, 2003, 198(12): 1951-1957.
85.	Kelchtermans H, Geboes L, Mitera T, et al. Activated CD4+CD25+ regulatory T cells inhibit osteoclastogenesis and collagen-induced arthritis[J]. Annals of the rheumatic diseases, 2009, 68(5): 744-750.
86.	Delgado M, Toscano MG, Benabdellah K, et al. In vivo delivery of lentiviral vectors expressing vasoactive intestinal peptide complementary DNA as gene therapy for collagen-induced arthritis[J]. Arthritis and rheumatism, 2008, 58(4): 1026-1037.
87.	Seki M, Oomizu S, Sakata KM, et al. Galectin-9 suppresses the generation of Th17, promotes the induction of regulatory T cells, and regulates experimental autoimmune arthritis[J]. Clin Immunol, 2008, 127(1): 78-88.
88.	Gonzalez-Rey E, Chorny A, Varela N, et al. Therapeutic effect of urocortin on collagen-induced arthritis by down-regulation of inflammatory and Th1 responses and induction of regulatory T cells[J]. Arthritis and rheumatism, 2007, 56(2): 531-543.
89.	Sonderegger I, Rohn TA, Kurrer MO, et al. Neutralization of IL-17 by active vaccination inhibits IL-23-dependent autoimmune myocarditis[J]. European journal of immunology, 2006, 36(11): 2849-2856.

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.
30. 　Zheng SG, Wang JH, Koss MN, et al. CD4+ and CD8+ regulatory T cells generated ex vivo with IL-2 and TGF-beta suppress a stimulatory graft-versus-host disease with a lupus-like syndrome[J]. J Immunol, 2004, 172(3): 1531-1539.
31. 　Tran DQ, Ramsey H, Shevach EM. Induction of FOXP3 expression in naive human CD4+FOXP3 T cells by T-cell receptor stimulation is transforming growth factor-beta dependent but does not confer a regulatory phenotype[J]. Blood, 2007, 110(8): 2983-2990.
32. 　Collison LW, Workman CJ, Kuo TT, et al. The inhibitory cytokine IL-35 contributes to regulatory T-cell function[J]. Nature, 2007, 450(7169): 566-569.
33. 　Zheng Y, Josefowicz SZ, Kas A, et al. Genome-wide analysis of Foxp3 target genes in developing and mature regulatory T cells[J]. Nature, 2007, 445(7130): 936-940.
34. 　Wolf SF, Temple PA, Kobayashi M, et al. Cloning of cDNA for natural killer cell stimulatory factor, a heterodimeric cytokine with multiple biologic effects on T and natural killer cells[J]. J Immunol, 1991, 146(9): 3074-3081.
35. 　Allan SE, Song-Zhao GX, Abraham T, et al. Inducible reprogramming of human T cells into Treg cells by a conditionally active form of FOXP3[J]. European journal of immunology, 2008, 38(12): 3282-3289.
36. 　Chaturvedi V, Collison LW, Guy CS, et al. Cutting edge: Human regulatory T cells require IL-35 to mediate suppression and infectious tolerance[J]. J Immunol, 2011, 186(12): 6661-6666.
37. 　Morgan ME, Flierman R, van Duivenvoorde LM, et al. Effective treatment of collagen-induced arthritis by adoptive transfer of CD25+ regulatory T cells[J]. Arthritis and rheumatism, 2005, 52(7): 2212-2221.
38. 　Morgan ME, Sutmuller RP, Witteveen HJ, et al. CD25+ cell depletion hastens the onset of severe disease in collagen-induced arthritis[J]. Arthritis and rheumatism, 2003, 48(5): 1452-1460.
39. 　Gonzalez-Rey E, Fernandez-Martin A, Chorny A, et al. Vasoactive intestinal peptide induces CD4+,CD25+ T regulatory cells with therapeutic effect in collagen-induced arthritis[J]. Arthritis and rheumatism, 2006, 54(3): 864-876.
40. 　Niedbala W, Wei XQ, Cai B, et al. IL-35 is a novel cytokine with therapeutic effects against collagen-induced arthritis through the expansion of regulatory T cells and suppression of Th17 cells[J]. European journal of immunology, 2007, 37(11): 3021-3029.
41. 　Schottelius AJ, Mayo MW, Sartor RB, et al. Interleukin-10 signaling blocks inhibitor of kappaB kinase activity and nuclear factor kappaB DNA binding[J]. The Journal of biological chemistry, 1999, 274(45): 31868-31874.
42. 　Collison LW, Pillai MR, Chaturvedi V, et al. Regulatory T cell suppression is potentiated by target T cells in a cell contact, IL-35- and IL-10-dependent manner[J]. J Immunol, 2009, 182(10): 6121-6128.
43. 　Mottet C, Uhlig HH, Powrie F. Cutting edge: cure of colitis by CD4+CD25+ regulatory T cells[J]. J Immunol, 2003, 170(8): 3939-3943.
44. 　Colgan J, Rothman P. All in the family: IL-27 suppression of T(H)-17 cells[J]. Nature immunology, 2006, 7(9): 899-901.
45. 　Niedbala W, Cai B, Liu H, et al. Nitric oxide induces CD4+CD25+ Foxp3 regulatory T cells from CD4+CD25 T cells via p53, IL-2, and OX40[J]. Proceedings of the National Academy of Sciences of the United States of America, 2007, 104(39): 15478-15483.
46. 　Lund JM, Hsing L, Pham TT, et al. Coordination of early protective immunity to viral infection by regulatory T cells[J]. Science, 2008, 320(5880): 1220-1224.
47. 　Haribhai D, Lin W, Relland LM, et al. Regulatory T cells dynamically control the primary immune response to foreign antigen[J]. J Immunol, 2007, 178(5): 2961-2972.
48. 　Kim JM, Rasmussen JP, Rudensky AY. Regulatory T cells prevent catastrophic autoimmunity throughout the lifespan of mice[J]. Nature immunology, 2007, 8(2): 191-197.
49. 　Kassiotis G, O’Garra A. Immunology. Immunity benefits from a little suppression[J]. Science, 2008, 320(5880): 1168-1169.
50. 　Kempe S, Heinz P, Kokai E, et al. Epstein-barr virus-induced gene-3 is expressed in human atheroma plaques[J]. The American journal of pathology, 2009, 175(1): 440-447.
51. 　Hsieh CS, Liang Y, Tyznik AJ, et al. Recognition of the peripheral self by naturally arising CD25+ CD4+ T cell receptors[J]. Immunity, 2004, 21(2): 267-277.
52. 　Pacholczyk R, Ignatowicz H, Kraj P, et al. Origin and T cell receptor diversity of Foxp3+CD4+CD25+ T cells[J]. Immunity, 2006, 25(2): 249-259.
53. 　Almeida AR, Zaragoza B, Freitas AA. Indexation as a novel mechanism of lymphocyte homeostasis: the number of CD4+CD25+ regulatory T cells is indexed to the number of IL-2-producing cells[J]. J Immunol, 2006, 177(1): 192-200.
54. 　Bettelli E, Carrier Y, Gao W, et al. Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells[J]. Nature, 200, 441(7090): 235-238.
55. 　Harrington LE, Hatton RD, Mangan PR, et al. Interleukin 17-producing CD4+ effector T cells develop via a lineage distinct from the T helper type 1 and 2 lineages[J]. Nature immunology, 2005, 6(11): 1123-1132.
56. 　Wahl SM, Wen J, Moutsopoulos N. TGF-beta: a mobile purveyor of immune privilege[J]. Immunological reviews, 2006, 213: 213-227.
57. 　Park H, Li Z, Yang XO, et al. A distinct lineage of CD4 T cells regulates tissue inflammation by producing interleukin 17[J]. Nature immunology, 2005, 6(11): 1133-1141.
58. 　Kolls JK, Linden A. Interleukin-17 family members and inflammation[J]. Immunity, 2004, 21(4): 467-476.
59. 　Langrish CL, Chen Y, Blumenschein WM, et al. IL-23 drives a pathogenic T cell population that induces autoimmune inflammation[J]. The Journal of experimental medicine, 2005, 201(2): 233-240.
60. 　Ivanov, II, McKenzie BS, Zhou L, et al. The orphan nuclear receptor RORgammat directs the differentiation program of proinflammatory IL-17+ T helper cells[J]. Cell, 2006, 126(6): 1121-1133.
61. 　Yang J, Yang M, Htut TM, et al. Epstein-Barr virus-induced gene 3 negatively regulates IL-17, IL-22 and RORgamma t[J]. European journal of immunology, 2008, 38(5): 1204-1214.
62. 　Steinman L. Multiple sclerosis: a coordinated immunological attack against myelin in the central nervous system[J]. Cell, 1996, 85(3): 299-302.
63. 　Zheng Y, Rudensky AY. Foxp3 in control of the regulatory T cell lineage[J]. Nature immunology, 2007, 8(5): 457-462.
64. 　Adorini L. Interleukin-12, a key cytokine in Th1-mediated autoimmune diseases[J]. Cellular and molecular life sciences : CMLS, 1999, 55(12): 1610-1625.
65. 　Karp CL, Biron CA, Irani DN. Interferon beta in multiple sclerosis: is IL-12 suppression the key? [J]Immunology today, 2000, 21(1): 24-28.
66. 　Constantinescu CS, Wysocka M, Hilliard B, et al. Antibodies against IL-12 prevent superantigen-induced and spontaneous relapses of experimental autoimmune encephalomyelitis[J]. J Immunol, 1998, 161(9): 5097-5104.
67. 　Leonard JP, Waldburger KE, Goldman SJ. Prevention of experimental autoimmune encephalomyelitis by antibodies against interleukin 12[J]. The Journal of experimental medicine, 1995, 181(1): 381-386.
68. 　Costa GL, Sandora MR, Nakajima A, et al. Adoptive immunotherapy of experimental autoimmune encephalomyelitis via T cell delivery of the IL-12 p40 subunit[J]. J Immunol, 2001, 167(4): 2379-2387.
69. 　Becher B, Durell BG, Noelle RJ. Experimental autoimmune encephalitis and inflammation in the absence of interleukin-12[J]. The Journal of clinical investigation, 2002, 110(4): 493-497.
70. 　Gran B, Zhang GX, Yu S, et al. IL-12p35-deficient mice are susceptible to experimental autoimmune encephalomyelitis: evidence for redundancy in the IL-12 system in the induction of central nervous system autoimmune demyelination[J]. J Immunol, 2002, 169(12): 7104-7110.
71. 　Cua DJ, Sherlock J, Chen Y, et al. Interleukin-23 rather than interleukin-12 is the critical cytokine for autoimmune inflammation of the brain[J]. Nature, 2003, 421(6924): 744-748.
72. 　Aggarwal S, Ghilardi N, Xie MH, et al. Interleukin-23 promotes a distinct CD4 T cell activation state characterized by the production of interleukin-17[J]. The Journal of biological chemistry, 2003, 278(3): 1910-1914.
73. 　Nagai T, Devergne O, van Seventer GA, et al. Interferon-beta mediates opposing effects on interferon-gamma-dependent Interleukin-12 p70 secretion by human monocyte-derived dendritic cells[J]. Scandinavian journal of immunology, 2007, 65(2): 107-117.
74. 　Goldberg R, Zohar Y, Wildbaum G, et al. Suppression of ongoing experimental autoimmune encephalomyelitis by neutralizing the function of the p28 subunit of IL-27[J]. J Immunol, 2004, 173(10): 6465-6471.
75. 　Kohm AP, Carpentier PA, Anger HA, et al. Cutting edge: CD4+CD25+ regulatory T cells suppress antigen-specific autoreactive immune responses and central nervous system inflammation during active experimental autoimmune encephalomyelitis[J]. J Immunol, 2002, 169(9): 4712-4716.
76. 　McHugh RS, Shevach EM. The role of suppressor T cells in regulation of immune responses[J]. The Journal of allergy and clinical immunology, 2002, 110(5): 693-702.
77. 　McGeachy MJ, Stephens LA, Anderton SM. Natural recovery and protection from autoimmune encephalomyelitis: contribution of CD4+CD25+ regulatory cells within the central nervous system[J]. J Immunol, 2005, 175(5): 3025-3032.
78. 　Neu N, Rose NR, Beisel KW, et al. Cardiac myosin induces myocarditis in genetically predisposed mice[J]. J Immunol, 1987, 139(11): 3630-3636.
79. 　Reddy J, Illes Z, Zhang X, et al. Myelin proteolipid protein-specific CD4+CD25+ regulatory cells mediate genetic resistance to experimental autoimmune encephalomyelitis[J]. Proceedings of the National Academy of Sciences of the United States of America, 2004, 101(43): 15434-15439.
80. 　Thakker P, Leach MW, Kuang W, et al. IL-23 is critical in the induction but not in the effector phase of experimental autoimmune encephalomyelitis[J]. J Immunol, 2007, 178(4): 2589-2598.
81. 　Courtenay JS, Dallman MJ, Dayan AD, et al. Immunisation against heterologous type II collagen induces arthritis in mice[J]. Nature, 1980, 283(5748): 666-668.
82. 　Lubberts E, van den Bersselaar L, Oppers-Walgreen B, et al. IL-17 promotes bone erosion in murine collagen-induced arthritis through loss of the receptor activator of NF-kappa B ligand/osteoprotegerin balance[J]. J Immunol, 2003, 170(5): 2655-2662.
83. 　Rohn TA, Jennings GT, Hernandez M, et al. Vaccination against IL-17 suppresses autoimmune arthritis and encephalomyelitis[J]. European journal of immunology, 2006, 36(11): 2857-2867.
84. 　Murphy CA, Langrish CL, Chen Y, et al. Divergent pro- and antiinflammatory roles for IL-23 and IL-12 in joint autoimmune inflammation[J]. The Journal of experimental medicine, 2003, 198(12): 1951-1957.
85. 　Kelchtermans H, Geboes L, Mitera T, et al. Activated CD4+CD25+ regulatory T cells inhibit osteoclastogenesis and collagen-induced arthritis[J]. Annals of the rheumatic diseases, 2009, 68(5): 744-750.
86. 　Delgado M, Toscano MG, Benabdellah K, et al. In vivo delivery of lentiviral vectors expressing vasoactive intestinal peptide complementary DNA as gene therapy for collagen-induced arthritis[J]. Arthritis and rheumatism, 2008, 58(4): 1026-1037.
87. 　Seki M, Oomizu S, Sakata KM, et al. Galectin-9 suppresses the generation of Th17, promotes the induction of regulatory T cells, and regulates experimental autoimmune arthritis[J]. Clin Immunol, 2008, 127(1): 78-88.
88. 　Gonzalez-Rey E, Chorny A, Varela N, et al. Therapeutic effect of urocortin on collagen-induced arthritis by down-regulation of inflammatory and Th1 responses and induction of regulatory T cells[J]. Arthritis and rheumatism, 2007, 56(2): 531-543.
89. 　Sonderegger I, Rohn TA, Kurrer MO, et al. Neutralization of IL-17 by active vaccination inhibits IL-23-dependent autoimmune myocarditis[J]. European journal of immunology, 2006, 36(11): 2849-2856.

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