山东大学耳鼻喉眼学报 ›› 2023, Vol. 37 ›› Issue (5): 156-161.doi: 10.6040/j.issn.1673-3770.0.2022.258

• 综述 • 上一篇    

TH2细胞因子在2型慢性鼻窦炎伴鼻息肉中的作用机制研究进展

朱玉,朱新华   

  1. 南昌大学第二附属医院 耳鼻咽喉头颈外科, 江西 南昌 330006
  • 发布日期:2023-10-13
  • 通讯作者: 朱新华. E-mail:zhuxinhua2003@126.com
  • 基金资助:
    国家自然科学基金项目(82060186);江西省自然科学基金项目(20202BABL206064)

Research progress on the role of TH2 cytokines in Type2 chronic rhinosinusitis with nasal polyps

ZHU Yu, ZHU Xinhua   

  1. Department of Otolaryngology Head and Neck Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi, China
  • Published:2023-10-13

摘要: 慢性鼻窦炎(chronic rhinosinusitis with nasal polyps, CRS)根据其发病机制可分为2型和非2型炎症内型,其中2型炎症对应于嗜酸性粒细胞浸润为主的慢性鼻窦炎伴鼻息肉(chronic rhinosinusitis with nasal polyps, CRSwNP)。典型的2型CRSwNP患者通常对目前的治疗有耐药性,表现出较高的复发率。尽管生物制剂在其治疗上取得了一定的成功,但靶向单一TH2细胞因子并不能完全消除大多数患者的2型疾病,故靶向阻断TH2细胞因子及其下游的信号转导通路可能是针对内型治疗的一种新思路。论文对各2型细胞因子(IL-4、IL-5、IL-9、IL-13、IL-25和IL-33)在2型CRSwNP中与其特异性受体相互结合后激活的细胞内信号通路进行综述,旨在为治疗2型CRSwNP提供新的靶点。

关键词: 慢性鼻窦炎, 鼻息肉, TH2细胞因子, 嗜酸性粒细胞, 信号转导通路

Abstract: Chronic rhinosinusitis(CRS)are classified as type 2 and non-type 2 intrainflammatory types according to the pathogenesis, where type 2 inflammation corresponds to chronic rhinosinusitis with nasal polyps(CRSwNP)dominated by eosinophil infiltration. Patients with typical type 2 CRSwNP are typically resistant to current treatments and exhibit high recurrence rates. Although some success has been achieved regarding treatment, targeting a single TH2 cytokine cannot completely eliminate type 2 CRSwNP in most patients. Therefore, targeting the TH2 cytokine and its downstream signal transduction pathway may present a novel approach for endotherapy. In this study, we review the intracellular signaling pathways activated by various type 2 cytokines(IL-4, IL-5, IL-9, IL-13, IL-25, and IL-33)after binding to their specific receptors in type 2 CRSwNP, in order to provide new targets for type 2 CRSwNP therapeutics.

Key words: Chronic rhinosinusitis, Nasal polyps, TH2 cytokines, Eosinophil, Signal transduction pathway

中图分类号: 

  • R765.4+1
[1] Fokkens WJ, Lund VJ, Hopkins C, et al. European position paper on rhinosinusitis and nasal polyps 2020[J]. Rhinology, 2020, 58(Suppl S29): 1-464. doi:10.4193/Rhin20.600
[2] Lee K, Tai JH, Lee SH, et al. Advances in the knowledge of the underlying airway remodeling mechanisms in chronic rhinosinusitis based on the endotypes: a review[J]. Int J Mol Sci, 2021, 22(2): 910. doi:10.3390/ijms22020910
[3] Wang XD, Zhang N, Bo MY, et al. Diversity of TH cytokine profiles in patients with chronic rhinosinusitis: a multicenter study in Europe, Asia, and Oceania[J]. J Allergy Clin Immunol, 2016, 138(5): 1344-1353. doi:10.1016/j.jaci.2016.05.041
[4] Busse WW, Kraft M, Rabe KF, et al. Understanding the key issues in the treatment of uncontrolled persistent asthma with type 2 inflammation[J]. Eur Respir J, 2021, 58(2): 2003393. doi:10.1183/13993003.03393-2020
[5] Avdeeva K, Fokkens W. Precision medicine in chronic rhinosinusitis with nasal polyps[J]. Curr Allergy Asthma Rep, 2018, 18(4): 25. doi:10.1007/s11882-018-0776-8
[6] Md SA, Md KJ, Thibaut van Zele MD P, et al. Endoscopic sinus surgery for type-2 CRS wNP: an endotype-based retrospective study[J]. Laryngoscope, 2019, 129(6): 1286-1292. doi:10.1002/lary.27815
[7] 陶丹丹, 董红军, 褚云锋, 等. 慢性鼻-鼻窦炎伴鼻息肉患者组织嗜酸性粒细胞与嗅觉功能障碍的相关性研究[J]. 山东大学耳鼻喉眼学报, 2020, 34(6): 16-20. doi:10.6040/j.issn.1673-3770.0.2019.388 TAO Dandan, DONG Hongjun, CHU Yunfeng, et al. Correlation between eosinophils and olfactory dysfunction in patients with CRSwNP after nasal operation[J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2020, 34(6): 16-20. doi:10.6040/j.issn.1673-3770.0.2019.388
[8] Gandhi NA, Bennett BL, Graham NMH, et al. Targeting key proximal drivers of type 2 inflammation in disease[J]. Nat Rev Drug Discov, 2016, 15(1): 35-50. doi:10.1038/nrd4624
[9] Kim HJ, Lim J, Jang YS, et al. Exogenous hydrogen peroxide induces lipid raft-mediated STAT-6 activation in T cells[J]. Cell Physiol Biochem, 2017, 42(6): 2467-2480. doi:10.1159/000480210
[10] Zhu JF. T helper 2(Th2)cell differentiation, type 2 innate lymphoid cell(ILC2)development and regulation of interleukin-4(IL-4)and IL-13 production[J]. Cytokine, 2015, 75(1): 14-24. doi:10.1016/j.cyto.2015.05.010
[11] Chen LQ, Grabowski KA, Xin JP, et al. IL-4 induces differentiation and expansion of Th2 cytokine-producing eosinophils[J]. J Immunol, 2004, 172(4): 2059-2066. doi:10.4049/jimmunol.172.4.2059
[12] Bal SM, Bernink JH, Nagasawa M, et al. IL-1β, IL-4 and IL-12 control the fate of group 2 innate lymphoid cells in human airway inflammation in the lungs[J]. Nat Immunol, 2016, 17(6): 636-645. doi:10.1038/ni.3444
[13] Poposki JA, Klingler AI, Tan BK, et al. Group 2 innate lymphoid cells are elevated and activated in chronic rhinosinusitis with nasal polyps[J]. Immun Inflamm Dis, 2017, 5(3): 233-243. doi:10.1002/iid3.161
[14] Fan GK, Wang HL, Takenaka H. Eosinophil infiltration and activation in nasal polyposis[J]. Acta Otolaryngol, 2007, 127(5): 521-526. doi:10.1080/00016480600951368
[15] Willebrand R, Dietschmann A, Nitschke L, et al. Murine eosinophil development and allergic lung eosinophilia are largely dependent on the signaling adaptor GRB2[J]. Eur J Immunol, 2018, 48(11): 1786-1795. doi:10.1002/eji.201847555
[16] Pelaia G, Vatrella A, Busceti MT, et al. Role of biologics in severe eosinophilic asthma-focus on reslizumab[J]. Ther Clin Risk Manag, 2016, 12: 1075-1082. doi:10.2147/TCRM.S111862
[17] Delemarre T, De Ruyck N, Holtappels G, et al. Unravelling the expression of interleukin-9 in chronic rhinosinusitis: a possible role for Staphylococcus aureus[J]. Clin Transl Allergy, 2020, 10(1): 41. doi:10.1186/s13601-020-00348-5
[18] Lin H, Lin D, Xiong XS, et al. Expression and regulation of interleukin-9 in chronic rhinosinusitis[J]. Am J Rhinol Allergy, 2015, 29(1): e18-e23. doi:10.2500/ajra.2015.29.4136
[19] Tsicopoulos A, Shimbara A, de Nadai P, et al. Involvement of IL-9 in the bronchial phenotype of patients with nasal polyposis[J]. J Allergy Clin Immunol, 2004, 113(3): 462-469. doi:10.1016/j.jaci.2003.12.009
[20] Shaw JL, Fakhri S, Citardi MJ, et al. IL-33-responsive innate lymphoid cells are an important source of IL-13 in chronic rhinosinusitis with nasal polyps[J]. Am J Respir Crit Care Med, 2013, 188(4): 432-439. doi:10.1164/rccm.201212-2227OC
[21] Yuan T, Zheng R, Liu J, et al. Role of yes-associated protein in interleukin-13 induced nasal remodeling of chronic rhinosinusitis with nasal polyps[J]. Allergy, 2021, 76(2): 600-604. doi:10.1111/all.14699
[22] Li X, Huang JC, Chen XH, et al. IL-19 induced by IL-13/IL-17A in the nasal epithelium of patients with chronic rhinosinusitis upregulates MMP-9 expression via ERK/NF-κB signaling pathway[J]. Clin Transl Allergy, 2021, 11(1): e12003. doi:10.1002/clt2.12003
[23] Jiao J, Duan S, Meng N, et al. Role of IFN-γ, IL-13, and IL-17 on mucociliary differentiation of nasal epithelial cells in chronic rhinosinusitis with nasal polyps[J]. Clin Exp Allergy, 2016, 46(3): 449-460. doi:10.1111/cea.12644
[24] Khalmuratova R, Lee MY, Park JW, et al. Evaluation of neo-osteogenesis in eosinophilic chronic rhinosinusitis using a nasal polyp murine model[J]. Allergy Asthma Immunol Res, 2020, 12(2): 306-321. doi:10.4168/aair.2020.12.2.306
[25] Khalmuratova R, Shin HW, Kim DW, et al. Interleukin(IL)-13 and IL-17A contribute to neo-osteogenesis in chronic rhinosinusitis by inducing RUNX2[J]. EBioMedicine, 2019, 46: 330-341. doi:10.1016/j.ebiom.2019.07.035
[26] PhD SMK, Bs IB, Ms HK, et al. Interleukin 13(IL-13)alters hypoxia-associated genes and upregulates CD73[J]. Int Forum Allergy Rhinol, 2020, 10(9): 1096-1102. doi:10.1002/alr.22630
[27] Huang ZQ, Liu J, Ong HH, et al. Interleukin-13 alters tight junction proteins expression thereby compromising barrier function and dampens Rhinovirus induced immune responses in nasal epithelium[J]. Front Cell Dev Biol, 2020, 8: 572749. doi:10.3389/fcell.2020.572749
[28] Schmidt H, Braubach P, Schilpp C, et al. IL-13 impairs tight junctions in airway epithelia[J]. Int J Mol Sci, 2019, 20(13): 3222. doi:10.3390/ijms20133222
[29] Lam EPS, Kariyawasam HH, Rana BMJ, et al. IL-25/IL-33-responsive TH2 cells characterize nasal polyps with a default TH17 signature in nasal mucosa[J]. J Allergy Clin Immunol, 2016, 137(5): 1514-1524. doi:10.1016/j.jaci.2015.10.019
[30] Luo XL, Li CL, Wang YM, et al. Interleukin-33 promotes Th2/Th17 response in eosinophilic and non-eosinophilic nasal polyps[J]. ORL J Otorhinolaryngol Relat Spec, 2020, 82(1): 34-39. doi:10.1159/000503976
[31] Iinuma T, Okamoto Y, Yamamoto H, et al. Interleukin-25 and mucosal T cells in noneosinophilic and eosinophilic chronic rhinosinusitis[J]. Ann Allergy Asthma Immunol, 2015, 114(4): 289-298. doi:10.1016/j.anai.2015.01.013
[32] Swaidani S, Bulek K, Kang ZZ, et al. T cell-derived Act1 is necessary for IL-25-mediated Th2 responses and allergic airway inflammation[J]. J Immunol, 2011, 187(6): 3155-3164. doi:10.4049/jimmunol.1002790
[33] Wu L, Zepp JA, Qian W, et al. A novel IL-25 signaling pathway through STAT5[J]. J Immunol, 2015, 194(9): 4528-4534. doi:10.4049/jimmunol.1402760
[34] Bachert C, Han JK, Desrosiers M, et al. Efficacy and safety of dupilumab in patients with severe chronic rhinosinusitis with nasal polyps(liberty np sinus-24 and liberty np sinus-52): results from two multicentre, randomised, double-blind, placebo-controlled, parallel-group phase 3 trials[J]. Lancet, 2019, 394(10209): 1638-1650. doi:10.1016/S0140-6736(19)31881-1
[35] Wang Q, Sun Q, Chen QG, et al. Efficacy and safety of anti-interleukin-5 therapies in chronic rhinosinusitis with nasal polyps: a systematic review and meta-analysis of randomized controlled trials[J]. Int Arch Allergy Immunol, 2022, 183(7): 732-743. doi:10.1159/000521859
[36] Lee MY, Kim DW, Shin HW. Targeting IL-25 as a novel therapy in chronic rhinosinusitis with nasal polyps[J]. Curr Opin Allergy Clin Immunol, 2017, 17(1): 17-22. doi:10.1097/ACI.0000000000000332
[37] Md YH J, Hyun-Jin Cho MD P, Md YJJ, et al. Therapeutic effects of intranasal tofacitinib on chronic rhinosinusitis with nasal polyps in mice[J]. Laryngoscope, 2021, 131(5): E1400-E1407. doi:10.1002/lary.29129
[1] 王明明,罗洋,贺少娟,张现兴,李学忠. 慢性鼻窦炎鼻息肉基底干细胞转录组生物信息学分析[J]. 山东大学耳鼻喉眼学报, 2023, 37(5): 6-15.
[2] 王丽雪,曾毅,王丽欣,彭先兵. 浸润毕罗芬明胶海绵在功能性鼻内镜鼻窦手术后应用效果的临床观察[J]. 山东大学耳鼻喉眼学报, 2023, 37(5): 16-25.
[3] 王晓嫒,张欠欠,程翔宇,李志鹏,张维天,叶海波. 翼管神经切断术治疗2型慢性鼻窦炎伴过敏性鼻炎的临床疗效分析[J]. 山东大学耳鼻喉眼学报, 2023, 37(5): 42-49.
[4] 崔宁,王云梦,杨景朴. 2型固有淋巴细胞在慢性鼻窦炎中的作用及调节机制研究进展[J]. 山东大学耳鼻喉眼学报, 2023, 37(4): 153-159.
[5] 袁玥,付圣尧,姜彦,陈敏. 细胞焦亡在慢性气道炎症性疾病中的研究进展[J]. 山东大学耳鼻喉眼学报, 2023, 37(4): 166-171.
[6] 敖天, 程雷. 慢性鼻窦炎伴鼻息肉的内型研究及其指导下的精准控制与治疗[J]. 山东大学耳鼻喉眼学报, 2022, 36(3): 7-14.
[7] 熊攀辉,沈暘,杨玉成. 基于表型和内在型的慢性鼻窦炎诊治进展[J]. 山东大学耳鼻喉眼学报, 2022, 36(3): 15-19.
[8] 姚爽,娄鸿飞. 慢性鼻窦炎的内在型研究进展及精准医疗[J]. 山东大学耳鼻喉眼学报, 2022, 36(3): 20-29.
[9] 梁旭,史丽. 慢性鼻窦炎生物靶向药物治疗的研究进展[J]. 山东大学耳鼻喉眼学报, 2022, 36(3): 30-35.
[10] 石帅,郑泉,程雷. 度普利尤单抗在慢性鼻窦炎伴鼻息肉治疗中的研究进展[J]. 山东大学耳鼻喉眼学报, 2022, 36(3): 36-42.
[11] 王欢,胡俐,余洪猛. 慢性鼻窦炎相关嗅觉功能障碍研究进展[J]. 山东大学耳鼻喉眼学报, 2022, 36(3): 43-49.
[12] 宜若男,陈福权. 嗜酸性粒细胞与嗅觉功能障碍[J]. 山东大学耳鼻喉眼学报, 2022, 36(3): 50-55.
[13] 谷钰,万鑫,肖自安. 中性粒细胞和嗜酸性粒细胞在慢性鼻窦炎中的相互影响及临床治疗思考[J]. 山东大学耳鼻喉眼学报, 2022, 36(3): 56-63.
[14] 林海,朱莹,张维天. 慢性鼻窦炎发病中离子通道作用研究进展[J]. 山东大学耳鼻喉眼学报, 2022, 36(3): 64-70.
[15] 乔新杰,赵玉林. 慢性鼻窦炎中上皮间质转化信号转导通路及其他相关因子的研究进展[J]. 山东大学耳鼻喉眼学报, 2022, 36(3): 71-77.
Viewed
Full text


Abstract

Cited

  Shared   
  Discussed   
No Suggested Reading articles found!