气道上皮及其源性细胞因子与哮喘:思考与展望

doi:10.6040/j.issn.1671-7554.0.2024.0121

摘要/Abstract

摘要： 气道上皮通过与免疫细胞的紧密互作精细调控并维持气道微环境的形成,在哮喘免疫病理进展过程中处于核心地位。气道上皮源性细胞因子被认为在触发和维持哮喘气道炎症中担任关键角色,成为目前哮喘新型药物研发的热门靶点。本文综述气道上皮及其源性细胞因子在哮喘中的作用及相关靶向药物研究进展,为相关研究提供新视角与新思考。

关键词: 气道上皮, 细胞因子, 哮喘, 靶向药物, 展望

Abstract: The airway epithelium plays a central role in the pathogenesis of asthma by tightly interacting with immune cells and finely regulating the formation of the airway microenvironment. Epithelial-derived cytokines have been recognized as key players in triggering and sustaining airway inflammation in asthma, making them attractive targets for the development of novel asthma drugs. This article provides an overview of the role of the airway epithelium and its derived cytokines in asthma, as well as the progress in research on targeted drugs, offering new perspectives and insights for related studies.

Key words: Airway epithelium, Cytokines, Asthma, Targeted medicine, Outlook

中图分类号:

R562

张锦涛,董亮. 气道上皮及其源性细胞因子与哮喘:思考与展望[J]. 山东大学学报 (医学版), 2024, 62(5): 1-6.

ZHANG Jintao, DONG Liang. Airway epithelium and epithelial-derived cytokines in asthma: reflection and outlook[J]. Journal of Shandong University (Health Sciences), 2024, 62(5): 1-6.

参考文献

[1] Albrecht M, Garn H, Buhl T. Epithelial-immune cell interactions in allergic diseases[J]. Eur J Immunol, 2024, 54(1): e2249982. doi: 10.1002/eji.202249982.
[2] Noureddine N, Chalubinski M, Wawrzyniak P. The role of defective epithelial barriers in allergic lung disease and asthma development[J]. J Asthma Allergy, 2022, 15: 487-504. doi: 10.2147/JAA.S324080.
[3] Chen CY, Wu KH, Guo BC, et al. Personalized medicine in severe asthma: from biomarkers to biologics[J]. Int J Mol Sci, 2023, 25(1): 182. doi: 10.3390/ijms25010182.
[4] Hellings PW, Steelant B. Epithelial barriers in allergy and asthma[J]. J Allergy Clin Immunol, 2020, 145(6): 1499-1509.
[5] Vieira Braga FA, Kar G, Berg M, et al. A cellular census of human lungs identifies novel cell states in health and in asthma[J]. Nat Med, 2019, 25(7): 1153-1163.
[6] Zhang N, Xu J, Jiang C, et al.Neuro-immune regulation in inflammation and airway remodeling of allergic asthma[J]. Front Immunol, 2022, 13: 894047. doi: 10.3389/fimmu.2022.894047.
[7] Kohanski MA, Workman AD, Patel NN, et al. Solitary chemosensory cells are a primary epithelial source of IL-25 in patients with chronic rhinosinusitis with nasal polyps[J]. J Allergy Clin Immunol, 2018, 142(2): 460-469.e7.
[8] Waghray A, Monga I, Lin B, et al. A deep lung cell atlas reveals cytokine-mediated lineage switching of a rare cell progenitor of the human airway epithelium[J]. bioRxiv, 2023. doi: 10.1101/2023.11.28.569028.
[9] Gauvreau GM, Obyrne PM, Boulet LP, et al. Effects of an anti-TSLP antibody on allergen-induced asthmatic responses[J]. N Engl J Med, 2014, 370(22): 2102-2110.
[10] Barlow JL, Peel S, Fox J, et al. IL-33 is more potent than IL-25 in provoking IL-13-producing nuocytes(type 2 innate lymphoid cells)and airway contraction[J]. J Allergy Clin Immunol, 2013, 132(4): 933-941.
[11] Duchesne M, Okoye I, Lacy P. Epithelial cell alarmin cytokines: frontline mediators of the asthma inflammatory response[J]. Front Immunol, 2022, 13: 975914. doi: 10.3389/fimmu.2022.975914.
[12] Liu T, Liu Y, Miller M, et al. Autophagy plays a role in FSTL1-induced epithelial mesenchymal transition and airway remodeling in asthma[J]. Am J Physiol Lung Cell Mol Physiol, 2017, 313(1): L27-L40.
[13] Zhang J, Zhang D, Pan Y, et al. The TL1A-DR3 axis in asthma: membrane-bound and secreted TL1A co-determined the development of airway remodeling[J]. Allergy Asthma Immunol Res, 2022, 14(2): 233-253.
[14] Liu F, Zhang J, Zhang D, et al. Follistatin-related protein 1 in asthma: miR-200b-3p interactions affect airway remodeling and inflammation phenotype[J]. Int Immunopharmacol, 2022, 109: 108793. doi: 10.1016/j.intimp.2022.108793.
[15] Guo Z, Wu J, Zhao J, et al. IL-33 promotes airway remodeling and is a marker of asthma disease severity[J]. J Asthma, 2014, 51(8): 863-869.
[16] Cao L, Liu F, Liu Y, et al. TSLP promotes asthmatic airway remodeling via p38-STAT3 signaling pathway in human lung fibroblast[J]. Exp Lung Res, 2018, 44(6): 288-301.
[17] Zhang J, Dong L. Status and prospects: personalized treatment and biomarker for airway remodeling in asthma[J]. J Thorac Dis, 2020, 12(10): 6090-6101.
[18] Andreasson LM, Dyhre-Petersen N, Hvidtfeldt M, et al. Airway hyperresponsiveness correlates with airway TSLP in asthma independent of eosinophilic inflammation[J]. J Allergy Clin Immunol, 2023: S0091-6749(23)02409-0. doi: 10.1016/j.jaci.2023.11.915.
[19] Chatziparasidis G, Bush A, Chatziparasidi MR, et al. Airway epithelial development and function: a key player in asthma pathogenesis?[J]. Paediatr Respir Rev, 2023, 47: 51-61. doi: 10.1016/j.prrv.2023.04.005.
[20] Frey A, Lunding LP, Ehlers JC, et al. More than just a barrier: the immune functions of the airway epithelium in asthma pathogenesis[J]. Front Immunol, 2020, 11: 761. doi: 10.3389/fimmu.2020.00761.
[21] Basil MC, Katzen J, Engler AE, et al. The cellular and physiological basis for lung repair and regeneration: past, present, and future[J]. Cell Stem Cell, 2020, 26(4): 482-502.
[22] Basil MC, Cardenas-Diaz FL, Kathiriya JJ, et al. Human distal airways contain a multipotent secretory cell that can regenerate alveoli[J]. Nature, 2022, 604(7904): 120-126.
[23] Smolinska S, Antolín-Amérigo D, Popescu FD, et al. Thymic stromal lymphopoietin(TSLP), its isoforms and the interplay with the epithelium in allergy and asthma[J]. Int J Mol Sci, 2023, 24(16): 12725. doi: 10.3390/ijms241612725.
[24] Chen W, Chen S, Yan C, et al. Allergen protease-activated stress granule assembly and gasdermin D fragmentation control interleukin-33 secretion[J]. Nat Immunol, 2022, 23(7): 1021-1030.
[25] Zhang D, Zhang J, Xu C, et al. A humanized mouse model to study asthmatic airway remodeling and Muc-5ac secretion via the human IL-33[J]. Allergy, 2024. 79(5): 1364-1367.
[26] Qi Q, Xu J, Wang Y, et al. Decreased sphingosine due to down-regulation of acid ceramidase expression in airway of bronchiectasis patients: a potential contributor to pseudomonas aeruginosa infection[J]. Infect Drug Resist, 2023, 16: 2573-2588. doi: 10.2147/IDR.S407335.
[27] Saikumar Jayalatha AK, Jonker MR, Carpaij OA, et al. Lack of a transcriptional response of primary bronchial epithelial cells from patients with asthma and controls to IL-33[J]. Am J Physiol Lung Cell Mol Physiol, 2024, 326(1): L65-L70.
[28] Ruhl A, Antão AV, Dietschmann A, et al. STAT6-induced production of mucus and resistin-like molecules in lung Club cells does not protect against helminth or influenza A virus infection[J]. Eur J Immunol, 2024, 54(1): e2350558. doi: 10.1002/eji.202350558.
[29] Li Y, Zhang Q, Li L, et al. LKB1 deficiency upregulates RELM-α to drive airway goblet cell metaplasia[J]. Cell Mol Life Sci, 2021, 79(1): 42. doi: 10.1007/s00018-021-04044-w.
[30] Kortekaas RK, Geillinger-Kästle KE, Borghuis T, et al. Interleukin-11 disrupts alveolar epithelial progenitor function[J]. ERJ Open Res, 2023, 9(3): 00679-2022. doi: 10.1183/23120541.00679-2022.
[31] Thomas D, Mcdonald VM, Pavord ID, et al. Asthma remission: what is it and how can it be achieved?[J]. Eur Respir J, 2022, 60(5): 2102583. doi: 10.1183/13993003.02583-2021.
[32] Mümmler C, Milger K. Biologics for severe asthma and beyond[J]. Pharmacol Ther, 2023, 252: 108551. doi: 10.1016/j.pharmthera.2023.108551.
[33] Chan R, Stewart K, Misirovs R, et al. Targeting downstream type 2 cytokines or upstream epithelial alarmins for severe asthma[J]. J Allergy Clin Immunol Pract, 2022, 10(6): 1497-1505.
[34] Shinkai M, Yabuta T. Tezepelumab: an anti-thymic stromal lymphopoietin monoclonal antibody for the treatment of asthma[J]. Immunotherapy, 2023, 15(17): 1435-1447.
[35] Wechsler ME, Ruddy MK, Pavord ID, et al. Efficacy and safety of itepekimab in patients with moderate-to-severe asthma[J]. N Engl J Med, 2021, 385(18): 1656-1668.
[36] Maspero J, Agache IO, Kamei T, et al. Long-term safety and exploratory efficacy of fevipiprant in patients with inadequately controlled asthma: the SPIRIT randomised clinical trial[J]. Respir Res, 2021, 22(1): 311. doi: 10.1186/s12931-021-01904-8.
[37] Eger K, Kroes JA, Ten Brinke A, et al. Long-term therapy response to anti-IL-5 biologics in severe asthma-a real-life evaluation[J]. J Allergy Clin Immunol Pract, 2021, 9(3): 1194-1200.
[38] Demarche SF, Schleich FN, Paulus VA, et al. Is it possible to claim or refute sputum eosinophils ≥ 3% in asthmatics with sufficient accuracy using biomarkers?[J]. Respir Res, 2017, 18(1): 133. doi: 10.1186/s12931-017-0615-9.
[39] Gautam S, Chu JH, Cohen AJ, et al. Sputum alarmins delineate distinct T2 cytokine pathways and unique subtypes of patients with asthma[J]. Allergy, 2023, 78(12): 3274-3277.
[40] Banno A, Reddy AT, Lakshmi SP, et al. Bidirectional interaction of airway epithelial remodeling and inflammation in asthma[J]. Clin Sci(Lond), 2020, 134(9): 1063-1079.
[41] Vannella KM, Ramalingam TR, Borthwick LA, et al. Combinatorial targeting of TSLP, IL-25, and IL-33 in type 2 cytokine-driven inflammation and fibrosis[J]. Sci Transl Med, 2016, 8(337): 337ra65. doi: 10.1126/scitranslmed.aaf1938.

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