国际口腔医学杂志

国际口腔医学杂志 ›› 2018, Vol. 45 ›› Issue (6): 716-722.doi: 10.7518/gjkq.2018.06.016

• 综述 • 上一篇    下一篇

白细胞介素-35及其与口腔疾病的关系

刘芳,蔡扬()   

  1. 贵州医科大学附属口腔医院牙周黏膜科 贵阳 550001
  • 收稿日期:2018-02-25 修回日期:2018-07-12 出版日期:2018-11-01 发布日期:2018-11-15
  • 通讯作者: 蔡扬
  • 作者简介:刘芳,住院医师,硕士,Email： 1047984284@qq.com
  • 基金资助:
    国家自然科学基金(81460104)

Interleukin-35 and its relationship with oral diseases

Fang Liu,Yang Cai()   

  1. Dept. of Periodontics & Oral Medicine, Stomatological Hospital of Guizhou Medical University, Guiyang 550001, China
  • Received:2018-02-25 Revised:2018-07-12 Online:2018-11-01 Published:2018-11-15
  • Contact: Yang Cai
  • Supported by:
    This study was supported by the National Natural Science Foundation of China(81460104)

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摘要：

白细胞介素（IL）-35是近年发现的主要由调节性T（Treg）细胞分泌的一种新型抑制性细胞因子,属于IL-12家族新成员。IL-35不仅可诱导一种新型Treg细胞或调节性B细胞的产生,而且还可抑制辅助性T（Th）17细胞和Th1细胞介导的炎性反应,从而在自身免疫性疾病、炎症性疾病及肿瘤等疾病的发生发展中起着重要的免疫调节作用。目前,IL-35已成为细胞因子研究的热点,为自身免疫性疾病、炎症性疾病等疾病的生物治疗提供了新方向。本文拟从IL-35的结构、生物学功能及其在口腔疾病中的研究进展作简要的综述。

关键词: 白细胞介素-35, 调节性T细胞, 免疫抑制

Abstract:

Interleukin (IL)-35 is a novel inhibitory cytokine produced by regulatory T (Treg) cells, which is the newest member of the IL-12 family of heterodimeric cytokines and offers the potential to be a target for new therapies for autoimmune, inflammatory, and infectious diseases. Unlike its proinflammatory relatives, IL-35 can contribute to the induction of new regulatory T and B cell populations and induce anti-inflammatory effects through inhibition of both T helper type 1 (Th1) and Th17 cells responses. IL-35 is likely to become a new cytokine research hotspot, for its role in oral diseases.

Key words: interleukin-35, regulatory T cell, immunosuppression

中图分类号: 

  • R781.5
[1] Pflanz S, Timans JC, Cheung J , et al. IL-27, a hetero-dimeric cytokine composed of EBI3 and p28 protein, induces proliferation of naive CD4 + T cells [J]. Im-munity, 2002,16(6):779-790.
doi: 10.1016/S1074-7613(02)00324-2 pmid: 12121660
[2] 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]. Eur J Immu- nol, 2007,37(11):3021-3029.
doi: 10.1002/eji.200737810 pmid: 17874423
[3] 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.
doi: 10.1038/nature06306 pmid: 18033300
[4] Collison LW, Vignali DA . Interleukin-35: odd one out or part of the family[J]. Immunol Rev, 2008,226:248-262.
doi: 10.1111/j.1600-065X.2008.00704.x pmid: 2631363
[5] Jones LL, Vignali DA . Molecular interactions within the IL-6/IL-12 cytokine/receptor superfamily[J]. Immunol Res, 2011,51(1):5-14.
doi: 10.1007/s12026-011-8209-y pmid: 3529148
[6] 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.
doi: 10.1016/S1074-7613(00)00070-4
[7] 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]. J Virol, 1996,70(2):1143-1153.
doi: 10.1016/0166-0934(95)01969-3 pmid: 8551575
[8] Hibbert L, Pflanz S , De Waal Malefyt R, et al. IL-27 and IFN-α signal via Stat1 and Stat3 and induce T-Bet and IL-12Rβ2 in naive T cells[J]. J Interferon Cytokine Res, 2003,23(9):513-522.
doi: 10.1089/10799900360708632
[9] Bardel E, Larousserie F, Charlot-Rabiega P , et al. Human CD4 + CD25 + Foxp3 + regulatory T cells do not constitutively express IL-35 [J]. J Immunol, 2008,181(10):6898-6905.
doi: 10.4049/jimmunol.181.10.6898 pmid: 18981109
[10] Seyerl M, Kirchberger S, Majdic O , et al. Human rhinoviruses induce IL-35-producing Treg via induc-tion of B7-H1 (CD274) and sialoadhesin (CD169) on DC[J]. Eur J Immunol, 2010,40(2):321-329.
doi: 10.1002/eji.v40:2
[11] Li X, Mai J, Virtue A , et al. IL-35 is a novel respon-sive anti-inflammatory cytokine—a new system of categorizing anti-inflammatory cytokines[J]. PLoS One, 2012,7(3):e33628.
doi: 10.1371/journal.pone.0033628
[12] Filková M, Vernerová Z, Hulejová H , et al. Pro-inflammatory effects of interleukin-35 in rheumatoid arthritis[J]. Cytokine, 2015,73(1):36-43.
doi: 10.1016/j.cyto.2015.01.019 pmid: 25697137
[13] Long J, Zhang X, Wen M , et al. IL-35 over-expression increases apoptosis sensitivity and suppresses cell growth in human cancer cells[J]. Biochem Biophys Res Commun, 2013,430(1):364-369.
doi: 10.1016/j.bbrc.2012.11.004 pmid: 23154182
[14] Presky DH, Yang H, Minetti LJ , et al. A functional interleukin 12 receptor complex is composed of two beta-type cytokine receptor subunits[J]. Proc Natl Acad Sci U S A, 1996,93(24):14002-14007.
doi: 10.1073/pnas.93.24.14002
[15] Chua AO, Wilkinson VL, Presky DH , et al. Cloning and characterization of a mouse IL-12 receptor-beta component[J]. J Immunol, 1995,155(9):4286-4294.
doi: 10.1089/jir.2007.0135 pmid: 7594587
[16] Collison LW, Delgoffe GM, Guy CS , et al. The composition and signaling of the IL-35 receptor are unconventional[J]. Nat Immunol, 2012,13(3):290-299.
doi: 10.1038/ni.2227 pmid: 3529151
[17] Wang RX, Yu CR, Dambuza IM , et al. Interleukin-35 induces regulatory B cells that suppress autoimmune disease[J]. Nat Med, 2014,20(6):633-641.
doi: 10.1038/nm.3554 pmid: 24743305
[18] Saito M, Yoshida K, Hibi M , et al. Molecular cloning of a murine IL-6 receptor-associated signal transducer, gp130, and its regulated expression in vivo[J]. J Im-munol, 1992,148(12):4066-4071.
pmid: 1602143
[19] Trinchieri G . Interleukin-12 and the regulation of innate resistance and adaptive immunity[J]. Nat Rev Immunol, 2003,3(2):133-146.
doi: 10.1038/nri1001 pmid: 12563297
[20] Chen Q, Ghilardi N, Wang H , et al. Development of Th1-type immune responses requires the type Ⅰ cy- tokine receptor TCCR[J]. Nature, 2000,407(6806):916-920.
[21] Kochetkova I, Golden S, Holderness K , et al. IL-35 stimulation of CD39 + regulatory T cells confers pro-tection against collagen Ⅱ-induced arthritis via the production of IL-10 [J]. J Immunol, 2010,184(12):7144-7153.
doi: 10.4049/jimmunol.0902739
[22] Collison LW, Chaturvedi V, Henderson AL , et al. IL-35-mediated induction of a potent regulatory T cell population[J]. Nat Immunol, 2010,11(12):1093-1101.
doi: 10.1038/ni.1952 pmid: 20953201
[23] Liu JQ, Liu Z, Zhang X , et al. Increased Th17 and regulatory T cell responses in EBV-induced gene 3- deficient mice lead to marginally enhanced develop- ment of autoimmune encephalomyelitis[J]. J Immunol, 2012,188(7):3099-3106.
doi: 10.4049/jimmunol.1100106 pmid: 22387555
[24] Wirtz S, Billmeier U, Mchedlidze T , et al. Interleu-kin-35 mediates mucosal immune responses that protect against T-cell-dependent colitis[J]. Gastroen-terology, 2011,141(5):1875-1886.
doi: 10.1053/j.gastro.2011.07.040 pmid: 3624892
[25] Bettini M, Castellaw AH, Lennon GP , et al. Preven-tion of autoimmune diabetes by ectopic pancreatic β-cell expression of interleukin-35[J]. Diabetes, 2012,61(6):1519-1526.
doi: 10.2337/db11-0784
[26] 施沛青, 朱书, 钱友存 . IL-17的信号传导及功能研究[J]. 中国细胞生物学学报, 2011,33(4):345-357.
Shi PQ, Zhu S, Qian YC . IL-17 signaling and func-tion[J]. Chin J Cell Biol, 2011,33(4):345-357.
[27] Yang J, Yang M, Htut TM , et al. Epstein-Barr virus-induced gene 3 negatively regulates IL-17, IL-22 and RORγt[J]. Eur J Immunol, 2008,38(5):1204-1214.
doi: 10.1002/(ISSN)1521-4141
[28] Huang CH, Loo EX, Kuo IC , et al. Airway inflam-mation and IgE production induced by dust mite allergen-specific memory/effector Th2 cell line can be effectively attenuated by IL-35[J]. J Immunol, 2011,187(1):462-471.
doi: 10.4049/jimmunol.1100259 pmid: 21613618
[29] Yoshizaki A, Miyagaki T , DiLillo DJ, et al. Regula-tory B cells control T-cell autoimmunity through IL- 21-dependent cognate interactions[J]. Nature, 2012,491(7423):264-268.
doi: 10.1038/nature11501
[30] Tirotta E, Duncker P, Oak J , et al. Epstein-Barr virus-induced gene 3 negatively regulates neuroinflamma-tion and T cell activation following coronavirus-induced encephalomyelitis[J]. J Neuroimmunol, 2013,254(1/2):110-116.
doi: 10.1016/j.jneuroim.2012.10.005
[31] 李姝文, 王秀敏, 李玉娟 . 寻常性银屑病患者外周血白介素27、白介素35及EBI3 mRNA表达的研究[J]. 中华皮肤科杂志, 2013,46(3):164-167.
doi: 10.3760/cma.j.issn.0412-4030.2013.03.005
Li SW, Wang XM, Li YJ . Expressions of interleu-kin-27, -35 and Epstein-Barr virus-induced gene 3 mRNA in peripheral blood of patients with psoriasis vulgaris[J]. Chin J Dermatol, 2013,46(3):164-167.
doi: 10.3760/cma.j.issn.0412-4030.2013.03.005
[32] Jafarzadeh A, Jamali M, Mahdavi R , et al. Circulating levels of interleukin-35 in patients with multiple sclerosis: evaluation of the influences of FOXP3 gene polymorphism and treatment program[J]. J Mol Neu-rosci, 2015,55(4):891-897.
doi: 10.1007/s12031-014-0443-z pmid: 25326790
[33] Ouyang H, Shi YB, Liu ZC , et al. Decreased inter-leukin 35 and CD4 +EBI3 + T cells in patients with active systemic lupus erythematosus [J]. Am J Med Sci, 2014,348(2):156-161.
doi: 10.1097/MAJ.0000000000000215 pmid: 25054737
[34] Yu W, Ge M, Lu S , et al. Anti-inflammatory effects of interleukin-35 in acquired aplastic anemia[J]. Cytokine, 2015,76(2):409-416.
doi: 10.1016/j.cyto.2015.08.004 pmid: 26282938
[35] Wang W, Li P, Chen YF , et al. A potential immuno-pathogenic role for reduced IL-35 expression in allergic asthma[J]. J Asthma, 2015,52(8):763-771.
doi: 10.3109/02770903.2015.1038390 pmid: 26044961
[36] Houshmandi N, Najafipour H, Joukar S , et al. The effect of interleukins 27 and 35 and their role on mediating the action of insulin like growth factor-1 on the inflammation and blood flow of chronically inflamed rat knee joint[J]. Cytokine, 2016,81:117-126.
doi: 10.1016/j.cyto.2016.03.010 pmid: 26994309
[37] Šenolt L, Šumová B, Jandová R , et al. Interleukin 35 synovial fluid levels are associated with disease ac-tivity of rheumatoid arthritis[J]. PLoS One, 2015,10(7):e0132674.
doi: 10.1371/journal.pone.0132674 pmid: 4512689
[38] Walton LJ, Macey MG, Thornhill MH , et al. Intra-epithelial subpopulations of T lymphocytes and Langerhans cells in oral lichen planus[J]. J Oral Pathol Med, 1998,27(3):116-123.
doi: 10.1111/j.1600-0714.1998.tb01926.x pmid: 9563803
[39] Piccinni MP, Lombardelli L, Logiodice F , et al. Potential pathogenetic role of Th17, Th0, and Th2 cells in erosive and reticular oral lichen planus[J]. Oral Dis, 2014,20(2):212-218.
doi: 10.1111/odi.12094 pmid: 23556506
[40] 刘芳 . 口腔扁平苔藓中Th17/Treg平衡与IL-35的相关性研究[D]. 贵阳: 贵州医科大学, 2016.
Liu F . Relativity analysis of Th17/Treg balance and IL-35 in oral lichen planus patients[D]. Guiyang: Guizhou Medical University, 2016.
[41] 黄韵颖 . IL-35对口腔扁平苔藓患者外周血Th17/Treg平衡的影响[D]. 贵阳: 贵州医科大学, 2017.
Huang YY . Effects of IL-35 on Th17/Treg balance in peripheral blood of patients with oral lichen planus[D]. Guiyang: Guizhou Medical University, 2017.
[42] Mitani A, Niedbala W, Fujimura T , et al. Increased expression of interleukin (IL)-35 and IL-17, but not IL-27, in gingival tissues with chronic periodontitis[J]. J Periodontol, 2015,86(2):301-309.
doi: 10.1902/jop.2014.140293
[43] Köseoğlu S, Sağlam M, Pekbağrıyanık T , et al. Level of Interleukin-35 in gingival crevicular fluid, saliva, and plasma in periodontal disease and health[J]. J Periodontol, 2015,86(8):964-971.
doi: 10.1902/jop.2015.140666 pmid: 2578656435
[44] 刘迪昕, 靳赢, 林晓萍 . IL-35在慢性牙周炎血清及龈沟液中的表达及相关性[J]. 上海口腔医学, 2015,24(4):455-459.
Liu DX, Jin Y, Lin XP . Expression and correlation of IL-35 in gingival crevicular fluid and serum with chronic periodontitis[J]. Shanghai J Stomatol, 2015,24(4):455-459.
[45] 麻婷婷, 王丽, 贾树芳 , 等. 牙周炎患者基础治疗前后龈沟液中IL-35浓度变化的研究[J]. 牙体牙髓牙周病学杂志, 2016,26(10):617-619.
doi: 10.15956/j.cnki.chin.j.conserv.dent.2016.10.008
Ma TT, Wang L, Jia SF , et al. Changes of IL-35 levels in giyngival crevicular fluid before and after basic periodontal treatment in periodontitis patients[J]. Chin J Conserv Dent, 2016,26(10):617-619.
doi: 10.15956/j.cnki.chin.j.conserv.dent.2016.10.008
[46] Wang HH, Liu CW, Li YC , et al. Efficacy of rituxi-mab for pemphigus: a systematic review and meta-analysis of different regimens[J]. Acta Derm Vene-reol, 2015,95(8):928-932.
doi: 10.2340/00015555-2116 pmid: 25881672
[47] Satyam A, Khandpur S, Sharma VK , et al. Involve-ment of TH1/TH2 cytokines in the pathogenesis of autoimmune skin disease—Pemphigus vulgaris[J]. Immunol Invest, 2009,38(6):498-509.
doi: 10.1080/08820130902943097
[48] Veldman C, Stauber A, Wassmuth R , et al. Dichotomy of autoreactive Th1 and Th2 cell responses to des-moglein 3 in patients with pemphigus vulgaris (PV) and healthy carriers of PV-associated HLA class Ⅱalleles[J]. J Immunol, 2003,170(1):635-642.
doi: 10.4049/jimmunol.170.1.635 pmid: 12496453
[49] Xu RC, Zhu HQ, Li WP , et al. The imbalance of Th17 and regulatory T cells in pemphigus patients[J]. Eur J Dermatol, 2013,23(6):795-802.
doi: 10.1684/ejd.2013.2177 pmid: 24192290
[50] Tavakolpour S, Kheiry F, Mirsafaei HS , et al. The possible role of interleukin-35 and its therapeutic potential in pemphigus[J]. Int Immunopharmacol, 2017,42:11-17.
doi: 10.1016/j.intimp.2016.11.005 pmid: 27855302
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