醫(yī)學(xué)免疫學(xué)課件：白細(xì)胞介素-17（IL-17）與炎癥性腸?。↖BD）

1、白細(xì)胞介素-17（IL-17）與炎癥性腸?。↖BD）IBD簡要介紹IL-17簡要介紹IL-17的作用復(fù)雜性小結(jié)與展望提綱Http:/detail/1063549.html炎癥性腸?。↖nflammatory Bowel Disease, IBD ）免疫介導(dǎo)種類：潰瘍性結(jié)腸炎（Ulcerative colitis）克羅恩病（Crohns disease CD）發(fā)病率正在升高并發(fā)癥多種因素 Joana Torres, MDa, Saurabh Mehandru, MDa, Prof Jean-Frdric Colombel, MDa, Prof Laurent Peyrin-Biroulet, M

2、Db. Crohns disease EB/OL /10.1016/S0140-6736(16)31711-1 2016-11-30/2016-12-22 Joana Torres, MDa, Saurabh Mehandru, MDa, Prof Jean-Frdric Colombel, MDa, Prof Laurent Peyrin-Biroulet, MDb. Crohns disease EB/OL /10.1016/S0140-6736(16)31711-1 2016-11-30/2016-12-22Th17International Journal of Oral Scienc

3、e (2014) 6, 125132; doi:10.1038/ijos.2014.48; published 8 August 2014The mucosal immune system in the oral cavityan orchestra of T cell diversityRui-QingWu1,2, Dun-FangZhang1,2, EricTu1, Qian-MingChen2 and WanJunChen1IL-17與IL-17家族1、六個IL-17家族成員: IL-17A (IL-17)、IL-17B、IL-17C、IL-17D、IL-17E (亦命名為IL-25)和

4、IL-17F。2、IL-17A是IL-17家族的原型,3、IL-17F與IL-17有最高的同源性4、促炎因子：IL-17E、IL-17F 保護性：IL-17B 復(fù)雜性：IL-17AFujino S，Andoh A，Bamba S，et al Increased expression of interleukin 17 in inflammatory bowel diseaseJ Gut，2003，52( 1) : 65-70IL-17的作用 part1：傳統(tǒng)認(rèn)知1、促炎因子對IL-17功能的調(diào)節(jié)機制新進展1、泛素連接酶ubiquitin ligase：ItchMahesh Kathania1,

5、5, Prashant Khare1,5, Minghui Zeng1, Brandi Cantarel2, Haiying Zhang3, Hideki Ueno4 &K Venuprasad. Itch inhibits IL-17-mediated colon inflammation and tumorigenesis by ROR-t ubiquitination Jnature immunology,2016,17(8)：997-10042、補體的激活活化IL-1/IL-17A軸，并促進與結(jié)腸炎相關(guān)的腫瘤發(fā)生C Ning, Y-Y Li, Y Wang, G-C Han, R-X

6、Wang, H Xiao, et al. ChenComplement activation promotes colitis-associated carcinogenesis through activating intestinal IL-1b/IL-17A axis J Mucosal immunology,2015,8(6)1275-12843、microRNA miR-210對于TH17分化的調(diào)控；4、TRIF（TIR-domain-containing adapter-inducinginterferon-）Haopeng Wang1,5, Henrik Flach1,5, Mi

7、chio Onizawa2, Lai Wei3, Michael T McManus4 & Arthur Weiss. Negative regulation of Hif1a expression and TH17 differentiation by the hypoxia-regulated microRNA miR-210 Jnature immunology,2014,15(4)：393-401S Kanagavelu, C Flores, JM Termini, R Riveron, L Romero, K Chung, et al.TIR-domain-containing ad

8、apter-inducing interferon- (TRIF) regulates Th17-mediated intestinal immunopathology in colitisJ nature, 2015,8(2):96-306將已知促炎機理應(yīng)用于治療？Anti-IL17：secukinumab使用Secukinumab治療銀屑病性關(guān)節(jié)炎（PsA）Iain B McInnes, Joachim Sieper, Jrgen Braun, Paul Emery,Dsire van der Heijde, John D Isaacs. Efficacy and safety of se

9、cukinumab, a fully human anti-interleukin-17A monoclonal antibody, in patients with moderate-to-severe psoriatic arthritis: a 24-week, randomised, double-blind, placebo-controlled, phase II proof-of-concept trialJ Ann Rheum Dis 2014,73:349-356Mean (SE) Crohns Disease Activity Index score over time.W

10、olfgang Hueber, Bruce E Sands, Steve Lewitzky, Marc Vandemeulebroecke, Walter Reinisch, Peter D R Higgins. Secukinumab, a human anti-IL-17A monoclonal antibody, for moderate to severe Crohns disease: unexpected results of a randomised, double-blind placebo-controlled trial JGut,2012,61(12):1693-1700

11、IL-17作用的復(fù)雜性新認(rèn)知：1、IL-17調(diào)節(jié)Th12、IL-17抗菌感染的作用3、IL-17對防御與屏障的保持保護作用IL-17調(diào)節(jié)Th1OConnor W, Jr., Kamanaka M, Booth CJ, Town T, Nakae S, Iwakura Y, et al. A protective function for interleukin 17A in T cell-mediated intestinal inflammation. Nat Immunol 2009; 10(6): 603-9CD45RBhi CD25CD4+ T cells from Il17a/ mi

12、ce or wild-type mice into Rag1/ recipients慢性皮膚黏膜念珠菌?。阂赘腥巳和庵苎獑蝹€核細(xì)胞表達(dá)IL-17在mRNA水平和蛋白質(zhì)水平明顯低于健康人群白色念珠菌：口部殺滅真菌的免疫反應(yīng)：招募中性粒細(xì)胞；缺乏Th17的正常免疫反應(yīng)者易感IL-17抗菌感染的作用IL-17維持防御、屏障（1）IL-17可以與IL-22協(xié)同合成抗菌肽：IL-22也是TH17產(chǎn)生的一種炎癥因子，在體外與體內(nèi)常常與IL-17A、IL-17F共表達(dá)（2）TH17維持腸道穩(wěn)態(tài)：在缺乏Th17細(xì)胞的小鼠中，腸道細(xì)菌荷載量顯著上升（3）IL-17保護屏障作用（3）IL-17保護屏障作用Wu,

13、Wei, Chen, Feidi,Liu, Zhanju,Cong, Yingzi. Microbiota-specific Th17 Cells: Yin and Yang in Regulation of Inflammatory Bowel Disease JInflammatory bowel disease. 2016,22(6):14731482Lee JS, Tato CM, Joyce-Shaikh B, et al. Interleukin-23-independent IL-17 production regulates intestinal epithelial perm

14、eability. Immunity. 2015;43:727738IL-17與細(xì)胞間緊密連接Xinyang Song, Dai Dai, Xiao He, Shu Zhu, Yikun Yao, Hanchao Gao et al. Growth Factor FGF2 Cooperates with Interleukin-17 to Repair Intestinal Epithelial DamageJ immunity, 2015,43:488-501FGF2與IL-17的協(xié)同作用Xinyang Song, Dai Dai, Xiao He, Shu Zhu, Yikun Yao,

15、Hanchao Gao et al. Growth Factor FGF2 Cooperates with Interleukin-17 to Repair Intestinal Epithelial DamageJ immunity, 2015,43:488-501FGF2與IL-17的協(xié)同作用IL-17作用的兩面性IBD中的保護作用1、IL-17調(diào)節(jié)Th12、IL-17抗菌感染的作用3、IL-17對防御與屏障的保持促進細(xì)胞的增殖再生維持緊密連接促進sIgA的作用等總結(jié)與展望忽視重視促炎保護參考文獻(xiàn)1 Joana Torres, Saurabh Mehandru, Prof Jean-Frd

16、ric Colombel, Prof Laurent Peyrin-Biroulet. Crohns disease EB/OL http:/10.1016/S0140-6736(16)31711-1 2016-11-30/2016-12-222 Ryan Ungaro, Saurabh Mehandru, Patrick B Allen, Laurent Peyrin-Biroulet, Jean-Frdric Colombel. Ulcerative colitisEB/OL /10.1016/S0140-6736(16)32126-2,2016-11-30/2016-12-223 Lau

17、rent Beaugerie, Steven H. Itzkowitz, et al.Cancers Complicating Inflammatory Bowel DiseaseJ N Engl J Med, 2015, 372:1441-14524施沛青,朱書,錢友存.IL-17的信號傳導(dǎo)及功能研究J中國細(xì)胞生物學(xué)學(xué)報, 2011, 33(4): 345-3575Fujino S，Andoh A，Bamba S，et al Increased expression of interleukin 17 in inflammatory bowel diseaseJ Gut，2003，52( 1

18、) : 65-706 Sarah L. Gaffen, Renu Jain, Abhishek V. Garg and Daniel J. Cua.The IL23IL17 immune axis: frommechanisms to therapeutic testingJNATURE REVIEWS IMMUNOLOGY,2014,14:585-6007 Mahesh Kathania, Prashant Khare, Minghui Zeng, Brandi Cantarel, Haiying Zhang, Hideki Ueno &K Venuprasad. Itch inhibits

19、 IL-17-mediated colon inflammation and tumorigenesis by ROR-t ubiquitinationJnature immunology,2016,17(8)：997-10048 C Ning, Y-Y Li, Y Wang, G-C Han, R-X Wang, H Xiao, et al. ChenComplement activation promotes colitis-associated carcinogenesis through activating intestinal IL-1b/IL-17A axis J Mucosal

20、 immunology,2015,8(6)1275-12849 Haopeng Wang, Henrik Flach, Michio Onizawa, Lai Wei, Michael T McManus，Arthur Weiss. Negative regulation of Hif1a expression and TH17 differentiation by the hypoxia-regulated microRNA miR-210 Jnature immunology,2014,15(4)：393-40110 S Kanagavelu, C Flores, JM Termini,

21、R Riveron, L Romero, K Chung, et al.TIR-domain-containing adapter-inducing interferon- (TRIF) regulates Th17-mediated intestinal immunopathology in colitisJ nature, 2015,8(2):96-30611 Iain B McInnes, Joachim Sieper, Jrgen Braun, Paul Emery,Dsire van der Heijde, John D Isaacs. Efficacy and safety of

22、secukinumab, a fully human anti-interleukin-17A monoclonal antibody, in patients with moderate-to-severe psoriatic arthritis: a 24-week, randomised, double-blind, placebo-controlled, phase II proof-of-concept trialJ Ann Rheum Dis 2014,73:349-35612 Ogawa A, Andoh A, Araki Y et al. Neutralization of i

23、nterleukin-17 aggravates dextran sulfate sodium-induced colitis in miceJClin Immunol 2004;110:556213 Sands BE, Chen J, Penney M et al. Initial evaluation of MEDI2070 (specific anti-IL-23 antibody) in patients with active Crohns disease who have failed anti-TNF antibody therapy: a randomized, double-

24、blind placebo-controlled phase 2a induction studyJGastroenterology 2015;148(Suppl 1)S163S16413 Wolfgang Hueber, Bruce E Sands, Steve Lewitzky, Marc Vandemeulebroecke, Walter Reinisch, Peter D R Higgins. Secukinumab, a human anti-IL-17A monoclonal antibody, for moderate to severe Crohns disease: unex

25、pected results of a randomised, double-blind placebo-controlled trial JGut,2012,61(12):1693-170014 Wu, Wei, Chen, Feidi,Liu, Zhanju,Cong, Yingzi. Microbiota-specific Th17 Cells: Yin and Yang in Regulation of Inflammatory Bowel Disease JInflammatory bowel disease. 2016,22(6):1473148215 OConnor W, Jr.

26、, Kamanaka M, Booth CJ, Town T, Nakae S, Iwakura Y, et al. A protective function for interleukin 17A in T cell-mediated intestinal inflammationJ Nat Immunol,2009; 10(6): 603-916 Conti, H. R., Shen, F., Nayyar, N., Stocum, E., Sun, J. N., Lindemann, M. J. et al.Th17 cells and IL-17 receptor signaling

27、 are essential for mucosal host defense against oral candidiasisJJ. Exp. Med. 2009, 206:29931117 OQuinn DB, Palmer MT, Lee YK, Weaver CT. Emergence of the Th17 pathway and its role in host defenseJ Adv Immunol,2008, 99: 115-6318 Shih VF, Cox J, Kljavin NM, et al. Homeostatic IL-23 receptor signaling

28、 limits Th17 response through IL-22-mediated containment of commensal microbiotaJProc Natl Acad Sci U S A, 2014,111:139421394719 Lee JS, Tato CM, Joyce-Shaikh B, et al. Interleukin-23-independent IL-17 production regulates intestinal epithelial permeabilityJImmunity. 2015;43:72773820 Cao AT, Yao S, Gong B, et al. Th17 cells upregulate polymeric Ig receptor and intestinal IgA and contribute to intestinal homeostasis. J Immunol. 2012;189:4666467321 Janine Bilsborough , Stephan R. Targan ,Scott B. Snapper, Therapeutic Targets in Infl a