白细胞介素24在肺部相关疾病中的研究进展

doi:10.19983/j.issn.2096-8493.20250019

摘要/Abstract

摘要：

白细胞介素24(IL-24)是细胞因子IL-10家族的重要成员,广泛表达于免疫系统相关的组织和细胞中。在炎症或外界微环境刺激下,IL-24可通过在细胞内或分泌到细胞外与受体结合,激活STAT、ERK和SOCS等信号通路,促进免疫细胞的趋化和表达,参与多种肺部相关疾病的病理生理过程。IL-24的表达水平与非小细胞肺癌、肺纤维化、哮喘等肺部疾病相关,靶向IL-24及其受体能够减少疾病损伤和改善预后。本文主要介绍IL-24在肺部相关疾病中的研究进展,希望为探索其在疾病的作用机制及治疗提供参考。

关键词: 白细胞介素24(IL-24), 免疫调节, 肺部疾病, 综述

Abstract:

Interleukin-24 (IL-24), a key member of the IL-10 cytokine family, is widely expressed in immune system-related tissues and cells. In response to inflammatory conditions or external micro-environmental stimuli, IL-24 activates signaling pathways such as STAT, ERK, and SOCS, through binding to receptors either intracellularly or extracellularly after secretion. This activation promotes immune cells chemotaxis and expression, thereby contributing to the pathophysiological processes of various pulmonary diseases. Expression levels of IL-24 are associated with non-small cell lung cancer, pulmonary fibrosis, asthma and other lung-related disorders. Targeting IL-24 and its receptors has shown potential to mitigate disease progression and improve prognosis. This review highlights the latest research progress on IL-24 in pulmonary diseases, aiming to provide valuable insights into its mechanisms and therapeutic applications.

Key words: Interleukin-24 (IL-24), Immune regulation, Lung disease, Summarize

中图分类号:

R393.12
R563

朱梦阳, 肖漓, 张涛. 白细胞介素24在肺部相关疾病中的研究进展[J]. 结核与肺部疾病杂志, 2025, 6(4): 472-476. doi: 10.19983/j.issn.2096-8493.20250019

Zhu Mengyang, Xiao Li, Zhang Tao. Research progress on the role of interleukin-24 in lung-related diseases[J]. Journal of Tuberculosis and Lung Disease, 2025, 6(4): 472-476. doi: 10.19983/j.issn.2096-8493.20250019

图/表 1

参考文献 39

[1]	Feng K, Cen J, Zou X, et al. Novel insight into MDA-7/IL-24: A potent therapeutic target for autoimmune and inflammatory diseases. Clin Immunol, 2024, 266: 110322. doi:10.1016/j.clim.2024.110322.
[2]	Zhang K, Qu J, Deng S, et al. Serum IL-24 combined with CA 125 as screening and prognostic biomarkers for NSCLC. Cell Biol Int, 2024, 48(8): 1160-1168. doi:10.1002/cbin.12173.
[3]	Mitamura Y, Nunomura S, Furue M, et al. IL-24: A new player in the pathogenesis of pro-inflammatory and allergic skin diseases. Allergol Int, 2020, 69(3): 405-411. doi:10.1016/j.alit.2019.12.003. pmid: 31980374
[4]	Modi J, Roy A, Pradhan AK, et al. Insights into the Mechanisms of Action of MDA-7/IL-24: A Ubiquitous Cancer-Suppressing Protein. Int J Mol Sci, 2021, 23(1): 72. doi:10.3390/ijms23010072.
[5]	Emdad L, Bhoopathi P, Talukdar S, et al. Recent insights into apoptosis and toxic autophagy: The roles of MDA-7/IL-24, a multidimensional anti-cancer therapeutic. Semin Cancer Biol, 2020, 66: 140-154. doi:10.1016/j.semcancer.2019.07.013. pmid: 31356866
[6]	Shibata N, Ohashi Y, Tsukada A, et al. IL24 Expression in Synovial Myofibroblasts: Implications for Female Osteoarthritis Pain through Propensity Score Matching Analysis. Medicina (Kaunas), 2024, 60(5):741. doi:10.3390/medicina60050741.
[7]	Vesely MD, Christensen SR. Type 2 immunity to the rescue: enhancing antitumor immunity for skin cancer prevention. J Clin Invest, 2025, 135(1):e188018. doi:10.1172/JCI188018.
[8]	Cai Y, He C, Dai Y, et al. Spinal interleukin-24 contributes to neuropathic pain after peripheral nerve injury through interleukin-20 receptor 2 in mice. Exp Neurol, 2024, 372: 114643. doi:10.1016/j.expneurol.2023.114643.
[9]	An Q, Gu X, Jiang Y. The Role of Interleukin-24 and Downstream Pathways in Inflammatory and Autoimmune Diseases. Cell Biochem Biophys, 2024. doi:10.1007/s12013-024-01576-3.
[10]	Zhang K, Hu W, Li F, et al. IL-24 improves efficacy of CAR-T cell therapy by targeting stemness of tumor cells. Br J Cancer, 2024, 130(8):1337-1347. doi:10.1038/s41416-024-02601-1.
[11]	Miri SM, Pourhossein B, Hosseini SY, et al. Enhanced synergistic antitumor effect of a DNA vaccine with anticancer cytokine, MDA-7/IL-24, and immune checkpoint blockade. Virol J, 2022, 19(1): 106. doi:10.1186/s12985-022-01842-x. pmid: 35752792
[12]	Sie C, Kant R, Peter C, et al. IL-24 intrinsically regulates Th 17 cell pathogenicity in mice. J Exp Med, 2022, 219(8):e20212443. doi:10.1084/jem.20212443.
[13]	Chong WP, Mattapallil MJ, Raychaudhuri K, et al. The Cytokine IL-17A Limits Th17 Pathogenicity via a Negative Feedback Loop Driven by Autocrine Induction of IL-24. Immunity, 2020, 53(2): 384-97.e5. doi:10.1016/j.immuni.2020.06.022. pmid: 32673565
[14]	Zhang X, Hu C, Zhong Y, et al. Multifunctional Interleukin-24 Resolves Neuroretina Autoimmunity via Diverse Mechanisms. Int J Mol Sci, 2022, 23(19): 11988. doi:10.3390/ijms231911988.
[15]	Chen J, Zhang Y, Zhang H, et al. IL-24 is the key effector of Th 9 cell-mediated tumor immunotherapy. iScience, 2023, 26(9): 107531. doi:10.1016/j.isci.2023.107531.
[16]	Smith S, Lopez S, Kim A, et al. Interleukin 24: Signal Transduction Pathways. Cancers (Basel), 2023, 15(13):3365. doi:10.3390/cancers15133365.
[17]	Zhong Y, Zhang X, Chong W. Interleukin-24 Immunobiology and Its Roles in Inflammatory Diseases. Int J Mol Sci, 2022, 23(2): 627. doi:10.3390/ijms23020627.
[18]	Wang B, Xia Y, Zhou C, et al. CD4⁺ T helper 2 cell-macrophage crosstalk induces IL-24-mediated breast cancer suppression. JCI Insight, 2025, 10(1):e180962. doi:10.1172/jci.insight.180962.
[19]	Rao LZ, Wang Y, Zhang L, et al. IL-24 deficiency protects mice against bleomycin-induced pulmonary fibrosis by repressing IL-4-induced M2 program in macrophages. Cell Death Differ, 2021, 28(4): 1270-1283. doi:10.1038/s41418-020-00650-6.
[20]	Giaccone G, He Y. Current knowledge of small cell lung cancer transformation from non-small cell lung cancer. Semin Cancer Biol, 2023, 94: 1-10. doi:10.1016/j.semcancer.2023.05.006.
[21]	Panneerselvam J, Srivastava A, Mehta M, et al. IL-24 Inhibits Lung Cancer Growth by Suppressing GLI1 and Inducing DNA Damage. Cancers (Basel), 2019, 11(12):1879. doi:10.3390/cancers11121879.
[22]	Qu J, Xia Z, Liu Y, et al. Targeting Antheraea pernyi silk fibroin modified dual-gene coexpressing vector enhances gene transport and promotes lung tumor suppression. Int J Biol Macromol, 2024, 262(Pt 2): 130074. doi:10.1016/j.ijbiomac.2024.130074.
[23]	Niu L, Chen G, Feng Y, et al. Polyethylenimine-Modified Bombyx mori Silk Fibroin as a Delivery Carrier of the ING4-IL-24 Coexpression Plasmid. Polymers (Basel), 2021, 13(20):3592. doi:10.3390/polym13203592.
[24]	Ji T, Li H. T-helper cells and their cytokines in pathogenesis and treatment of asthma. Front Immunol, 2023, 14: 1149203. doi:10.3389/fimmu.2023.1149203.
[25]	Feng KN, Meng P, Zhang M, et al. IL-24 Contributes to Neutrophilic Asthma in an IL-17A-Dependent Manner and Is Suppressed by IL-37. Allergy Asthma Immunol Res, 2022, 14(5): 505-527. doi:10.4168/aair.2022.14.5.505.
[26]	Feng KN, Meng P, Zou XL, et al. IL-37 protects against airway remodeling by reversing bronchial epithelial-mesenchymal transition via IL-24 signaling pathway in chronic asthma. Respir Res, 2022, 23(1): 244. doi:10.1186/s12931-022-02167-7.
[27]	Luo M, Zhao F, Cheng H, et al. Macrophage polarization: an important role in inflammatory diseases. Front Immunol, 2024, 15:1352946. doi:10.3389/fimmu.2024.1352946.
[28]	冯康尼, 孟平, 张敏, 等. IL-24调控巨噬细胞极化介导气道炎症在过敏性哮喘小鼠中的作用. 中国病理生理杂志, 2022, 38(7): 1201-1209. doi:10.3969/j.issn.1000-4718.2022.07.007.
[29]	Pokhreal D, Crestani B, Helou DG. Macrophage Implication in IPF: Updates on Immune, Epigenetic, and Metabolic Pathways. Cells, 2023, 12(17):2193. doi:10.3390/cells12172193.
[30]	Xu Y, Lan P, Wang T. The Role of Immune Cells in the Pathogenesis of Idiopathic Pulmonary Fibrosis. Medicina (Kaunas), 2023, 59(11):1984. doi:10.3390/medicina59111984.
[31]	Schleich F, Bougard N, Moermans C, et al. Cytokine-targeted therapies for asthma and COPD. Eur Respir Rev, 2023, 32(168). doi:10.1183/16000617.0193-2022.
[32]	李蕊, 肖漓. 慢性阻塞性肺疾病急性加重相关的免疫细胞及因子研究进展. 解放军医学杂志, 2023, 48(11): 1353-1358.
[33]	Patel VK, Kokkinis S, De Rubis G, et al. Curcumin liposomes attenuate the expression of cigarette smoke extract-induced inflammatory markers IL-8 and IL-24 in vitro. Excli j, 2024, 23: 904-907. doi:10.17179/excli2024-7467. pmid: 39165583
[34]	Dankhara N, Holla I, Ramarao S, et al. Bronchopulmonary Dysplasia: Pathogenesis and Pathophysiology. J Clin Med, 2023, 12(13):4207. doi:10.3390/jcm12134207.
[35]	Zhang Z, Jiang J, Li Z, et al. The Change of Cytokines and Gut Microbiome in Preterm Infants for Bronchopulmonary Dysplasia. Front Microbiol, 2022, 13: 804887. doi:10.3389/fmicb.2022.804887.
[36]	Gao R, Li Z, Ai D, et al. Interleukin-24 as a Pulmonary Target Cytokine in Bronchopulmonary Dysplasia. Cell Biochem Biophys, 2021, 79(2): 311-320. doi:10.1007/s12013-021-00968-z. pmid: 33683657
[37]	Alsayed SSR, Gunosewoyo H. Tuberculosis: Pathogenesis, Current Treatment Regimens and New Drug Targets. Int J Mol Sci, 2023, 24(6):5202. doi:10.3390/ijms24065202.
[38]	Menezes ME, Bhoopathi P, Pradhan AK, et al. Role of MDA-7/IL-24 a Multifunction Protein in Human Diseases. Adv Cancer Res, 2018, 138:143-182. doi:10.1016/bs.acr.2018.02.005. pmid: 29551126
[39]	Kumar NP, Moideen K, Banurekha VV, et al. Modulation of Th1/Tc1 and Th17/Tc17 responses in pulmonary tuberculosis by IL-20 subfamily of cytokines. Cytokine, 2018, 108:190-196. doi:10.1016/j.cyto.2018.04.005. pmid: 29684756