基因IL33是白细胞介素1家族的一员,最初被认为是2型免疫反应的诱导因子,能够激活T辅助2(TH2)细胞和肥大细胞。然而,越来越多的证据表明,IL33还能够强有力地刺激2组固有淋巴细胞(ILC2s)、调节性T(Treg)细胞、TH1细胞、CD8+ T细胞和自然杀伤(NK)细胞。这种多效性特性使得IL33在组织代谢稳态、感染、炎症、癌症和神经系统疾病中发挥着重要作用[1]。
有研究表明,IL33基因的变异与过敏性鼻炎有关[2]。此外,IL33还能够通过调节巨噬细胞的代谢重编程来控制炎症的消散[3]。在胃癌发生过程中,WFDC2通过上调IL33的表达来促进癌前病变的形成[4]。氧化后的IL33能够通过ST2非依赖性的RAGE/EGFR信号通路促进慢性阻塞性肺疾病(COPD)的病理发展[5]。IL33和胸腺基质淋巴生成素(TSLP)是肺上皮损伤后释放的警报素,能够激活肥大细胞、嗜酸性粒细胞和2组固有淋巴细胞等免疫细胞,参与炎症反应。目前,针对TSLP和IL33的药物研发正在进行中,有望为哮喘和COPD的治疗提供新的策略[6]。此外,IL33基因多态性与肺癌风险相关[7]。
综上所述,基因IL33在多种生理和病理过程中发挥着重要作用。IL33通过多种途径调节免疫细胞的活化和功能,影响炎症反应的发生和发展。此外,IL33还参与组织代谢稳态的调节,影响癌症的发生和发展。针对IL33的药物研发有望为多种疾病的治疗提供新的策略。
参考文献:
1. Liew, Foo Yew, Girard, Jean-Philippe, Turnquist, Heth Roderick. 2016. Interleukin-33 in health and disease. In Nature reviews. Immunology, 16, 676-689. doi:10.1038/nri.2016.95. https://pubmed.ncbi.nlm.nih.gov/27640624/
2. Joob, Beuy, Wiwanitkit, Viroj. 2020. IL33 rs1342326 gene variation and allergic rhinitis. In Acta paediatrica (Oslo, Norway : 1992), 109, 2117. doi:10.1111/apa.15227. https://pubmed.ncbi.nlm.nih.gov/32053215/
3. Faas, Maria, Ipseiz, Natacha, Ackermann, Jochen, Schett, Georg, Krönke, Gerhard. 2021. IL-33-induced metabolic reprogramming controls the differentiation of alternatively activated macrophages and the resolution of inflammation. In Immunity, 54, 2531-2546.e5. doi:10.1016/j.immuni.2021.09.010. https://pubmed.ncbi.nlm.nih.gov/34644537/
4. Jeong, Haengdueng, Lee, Buhyun, Kim, Kwang H, Goldenring, James R, Nam, Ki Taek. 2021. WFDC2 Promotes Spasmolytic Polypeptide-Expressing Metaplasia Through the Up-Regulation of IL33 in Response to Injury. In Gastroenterology, 161, 953-967.e15. doi:10.1053/j.gastro.2021.05.058. https://pubmed.ncbi.nlm.nih.gov/34116028/
5. Strickson, Sam, Houslay, Kirsty F, Negri, Victor A, Romero Ros, Xavier, Cohen, E Suzanne. 2023. Oxidised IL-33 drives COPD epithelial pathogenesis via ST2-independent RAGE/EGFR signalling complex. In The European respiratory journal, 62, . doi:10.1183/13993003.02210-2022. https://pubmed.ncbi.nlm.nih.gov/37442582/
6. Calderon, Ariel A, Dimond, Colin, Choy, David F, Mohan, Divya, Chung, Kian Fan. 2023. Targeting interleukin-33 and thymic stromal lymphopoietin pathways for novel pulmonary therapeutics in asthma and COPD. In European respiratory review : an official journal of the European Respiratory Society, 32, . doi:10.1183/16000617.0144-2022. https://pubmed.ncbi.nlm.nih.gov/36697211/
7. Mei, Lijun, Huang, Chongya, Wang, Ajing, Zhang, Xian. 2019. Association between ADRB2, IL33, and IL2RB gene polymorphisms and lung cancer risk in a Chinese Han population. In International immunopharmacology, 77, 105930. doi:10.1016/j.intimp.2019.105930. https://pubmed.ncbi.nlm.nih.gov/31685439/