OX40/OX40L轴介导T细胞免疫参与口腔扁平苔藓病程的研究进展

doi:10.12016/j.issn.2096-1456.2022.07.010

摘要/Abstract

摘要：

口腔扁平苔藓（oral lichen planus,OLP）是一种发病机制尚不明确的、常见的口腔黏膜慢性疾病。T细胞的局部浸润在其病理过程中起关键作用。越来越多的研究支持辅助性T细胞（helper T cell,Th）如Th1/Th2、Th17/调节T细胞（regulatory T cells,Treg）及其相关细胞因子的失衡与OLP的发病进展密切相关。近年来研究显示,共刺激分子OX40（CD134）及其配体OX40L（CD252）在T细胞免疫应答过程中具有重要意义而受到关注,参与Th1/Th2、Th17/Treg的平衡调控,介导促炎和抗炎的失衡,影响多种自身免疫性疾病的发生发展。但目前缺乏OX40/OX40L轴介导OLP发病过程中T细胞亚群失衡作用机制的研究。因此,未来仍需要针对OX40/OX40L轴调控OLP中T细胞亚群平衡机制开展大样本的临床和体内外实验研究。

关键词: 辅助性T细胞, 共刺激分子, OX40/OX40L, 口腔扁平苔藓, 免疫学机制, 细胞因子, T细胞亚群, 免疫治疗, 靶向治疗

Abstract:

Oral lichen planus (OLP) is a common chronic disease of the oral mucosa with unclear pathogenesis. Local infiltration of T cells plays a key role in the pathological process of OLP. Increased evidence supports the notion that the imbalance of helper T cells (Th) 1/Th2 and Th17/regulatory T cells (Treg) and their related cytokines is closely related to the pathogenesis and progression of OLP. In recent years, studies have shown that OX40 (CD134) and its ligand OX40L (CD252) play an important role in the process of the T-cell immune response. They participate in the balance regulation of Th1/Th2 and Th17/Treg, mediate the imbalance of pro-inflammatory and anti-inflammatory, and affect the occurrence and development of a variety of autoimmune diseases. However, there is no direct evidence that the OX40/OX40L axis mediates the imbalance of T-cell subsets in the pathogenesis of OLP. Therefore, large sample clinical as well as in vitro and in vivo experimental studies on the mechanism by which the OX40/OX40L axis regulates the balance of T-cell subsets in OLP are still needed in the future.

Key words: helper T cells, costimulatory molecules, OX40/OX40L, oral lichen planus, immunological mechanism, cytokines, T cell subsets, immunotherapy, targeted therapy

中图分类号:

刘洋, 王兴, 张妮, 张芳. OX40/OX40L轴介导T细胞免疫参与口腔扁平苔藓病程的研究进展[J]. 口腔疾病防治, 2022, 30(7): 523-527.

LIU Yang, WANG Xing, ZHANG Ni, ZHANG Fang. Research progress on OX40/OX40L axis mediated T cell immunity in the course of oral lichen planus[J]. Journal of Prevention and Treatment for Stomatological Diseases, 2022, 30(7): 523-527.

参考文献 33

[1]	González-Moles M, Warnakulasuriya S, González-Ruiz I, et al. Worldwide prevalence of oral lichen planus: a systematic review and meta-analysis[J]. Oral Dis, 2021, 27(4): 813-828. doi: 10. 1111/odi.13323. DOI URL
[2]	Iocca O, Sollecito TP, Alawi F, et al. Potentially malignant disorders of the oral cavity and oral dysplasia: a systematic review and meta-analysis of malignant transformation rate by subtype[J]. Head Neck, 2020, 42(3): 539-555. doi: 10.1002/hed.26006. DOI URL
[3]	田原野, 唐瞻贵. CD4+T细胞平衡在口腔癌及癌前病损中的研究进展[J]. 口腔疾病防治, 2019, 27(2): 115-121. doi: 10.12016/j.issn.2096-1456.2019.02.010. DOI
	Tian YY, Tang ZG. Research progress on the CD4+ T cell balance in oral cancer and precancerous diseases[J]. J Prev Treat Stomatol Dis, 2019, 27(2): 115-121. doi: 10.12016/j.issn.2096-1456. 2019.02.010. DOI
[4]	Wang F, Zhang J, Zhou G. The mTOR-glycolytic pathway promotes T-cell immunobiology in oral lichen planus[J]. Immunobiology, 2020, 225(3): 151933. doi: 10.1016/j.imbio.2020.151933. DOI URL
[5]	Fu Y, Lin Q, Zhang Z, et al. Therapeutic strategies for the costimulatory molecule OX40 in T-cell-mediated immunity[J]. Acta Pharm Sin B, 2020, 10(3): 414-433. doi: 10.1016/j.apsb.2019.08.010. DOI URL
[6]	Willoughby J, Griffiths J, Tews I, et al. OX40: structure and function-what questions remain?[J]. Mol Immunol, 2017, 83: 13-22. doi: 10.1016/j.molimm.2017.01.006. DOI PMID
[7]	Lane P. Role of OX40 signals in coordinating CD4 T cell selection,migration,and cytokine differentiation in T helper(Th)1 and Th2 cells[J]. J Exp Med, 2000, 191(2): 201-206. doi: 10.1084/jem. 191.2.201. DOI PMID
[8]	Saravia J, Chapman NM, Chi Hongbo. Helper T cell differentiation[J]. Cell Mol Immunol, 2019, 16(7): 634-643. doi: 10.1038/s41423-019-0220-6. DOI PMID
[9]	Read KA, Powell MD, Sreekumar BK, et al. In vitro differentiation of effector CD4(+) T helper cell subsets[J]. Methods Mol Biol, 2019, 1960: 75-84. doi: 10.1007/978-1-4939-9167-9_6. DOI
[10]	Wei Z, Yuan J, Wang G, Ocansey DKW, Xu Z, Mao F. Regulatory effect of mesenchymal stem cells on t cell phenotypes in autoimmune diseases[J]. Stem Cells Int, 2021, 2021: 5583994. doi: 10.1155/2021/5583994. DOI
[11]	Wang L, Wu Wei, Chen JiJun, et al. MicroRNA microarray-based identification of involvement of miR-155 and miR-19a in development of oral lichen planus (OLP) by modulating Th1/Th2 balance via targeting eNOS and Toll-like receptor 2 (TLR2)[J]. Med Sci Monit, 2018, 24: 3591-3603. doi: 10.12659/MSM.907497. DOI URL
[12]	Wang H, Zhang D, Han Q, et al. Role of distinct CD4(+)T helper subset in pathogenesis of oral lichen planus[J]. J Oral Pathol Med, 2016, 45(6): 385-393. doi: 10.1111/jop.12405. DOI PMID
[13]	Sun A, Wu YH, Chang JYF, et al. FoxP3CD4, IFN-γCD4, and IFN-γCD8 cell levels in erosive and non-erosive types of oral lichen planus patients[J]. J Dent Sci, 2021, 16(2): 751-756. doi: 10.1016/j.jds.2021.01.005. DOI URL
[14]	Wei W, Sun Q, Deng YW, et al. Mixed and inhomogeneous expression profile of Th1/Th2 related cytokines detected by cytometric bead array in the saliva of patients with oral lichen planus[J]. Oral Surg Oral Med Oral Pathol Oral Radiol, 2018, 126(2): 142-151. doi: 10.1016/j.oooo.2018.02.013. DOI URL
[15]	Ma RJ, He MJ, Tan YQ, et al. Artemisinin and its derivatives: a potential therapeutic approach for oral lichen planus[J]. Inflamm Res, 2019, 68(4): 297-310. doi: 10.1007/s00011-019-01216-0. DOI URL
[16]	Wing JB, Tanaka A, Sakaguchi S. Human FOXP3(+) regulatory T cell heterogeneity and function in autoimmunity and cancer[J]. Immunity, 2019, 50(2): 302-316. doi: 10.1016/j.immuni.2019.01.020. DOI URL
[17]	Schreurs O, Karatsaidis A, Schenck K. Phenotypically non-suppressive cells predominate among FoxP3-positive cells in oral lichen planus[J]. J Oral Pathol Med, 2016, 45(10): 766-773. doi: 10.1111/jop.12447. DOI PMID
[18]	胡文芸, 黄韵颖, 柳汀, 等. 白细胞介素35对口腔扁平苔藓患者外周血辅助性T细胞17与调节性T细胞平衡的影响[J]. 中华口腔医学杂志, 2020, 55(2): 80-85. doi: 10.3760/cma.j.issn.1002-0098.2020.02.002. DOI
	Hu WY, Huang YY, Liu T, et al. Effects of interleukin-35 on the balance of helper T cell 17/regulatory T cell in peripheral blood of patients with oral lichen planus[J]. Zhonghua Kou Qiang Yi Xue Za Zhi, 2020, 55(2): 80-85. doi: 10.3760/cma.j.issn.1002-0098. 2020.02.002. DOI
[19]	Wang H, Bai J, Luo Z, et al. Overexpression and varied clinical significance of Th9 versus Th17 cells in distinct subtypes of oral lichen planus[J]. Arch Oral Biol, 2017, 80: 110-116. doi: 10.1016/j.archoralbio.2017.04.003. DOI PMID
[20]	Javvadi LR, Parachuru VP, Milne TJ, et al. Regulatory T-cells and IL17A(+) cells infiltrate oral lichen planus lesions[J]. Pathology, 2016, 48(6): 564-573. doi: 10.1016/j.pathol.2016.06.002. DOI URL
[21]	Zhang H, Li F, Cao J, et al. A chimeric antigen receptor with antigen-independent OX40 signaling mediates potent antitumor activity[J]. Sci Transl Med, 2021, 13(578): eaba7308. doi: 10.1126/scitranslmed.aba7308. DOI
[22]	Lv YW, Chen Y, Lv HT, et al. Kawasaki disease OX40-OX40L axis acts as an upstream regulator of NFAT signaling pathway[J]. Pediatr Res, 2019, 85(6): 835-840. doi: 10.1038/s41390-019-0312-0. DOI URL
[23]	Fouladi S, Masjedi M, Ghasemi R, et al. The in vitro impact of glycyrrhizic acid on CD4+ T lymphocytes through OX40 receptor in the patients with allergic rhinitis[J]. Inflammation, 2018, 41(5): 1690-1701. doi: 10.1007/s10753-018-0813-8. DOI URL
[24]	Huang L, Wang M, Yan Y, et al. OX40L induces helper T cell differentiation during cell immunity of asthma through PI3K/AKT and P38 MAPK signaling pathway[J]. J Transl Med, 2018, 16(1): 74. doi: 10.1186/s12967-018-1436-4. DOI
[25]	Wu Q, Tang Y, Hu X, et al. Regulation of Th1/Th2 balance through OX40/OX40L signalling by glycyrrhizic acid in a murine model of asthma[J]. Respirology, 2016, 21(1): 102-111. doi: 10. 1111/resp.12655. DOI URL
[26]	Huang L, Zhang X, Wang M, et al. Exosomes from thymic stromal lymphopoietin-activated dendritic cells promote Th2 differentiation through the OX40 ligand[J]. Pathobiology, 2019, 86: 111-117. doi: 10.1159/000493013. DOI PMID
[27]	Sitrin J, Suto E, Wuster A, et al. The OX40/OX40 ligand pathway promotes pathogenic Th cell responses, plasmablast accumulation, and lupus nephritis in NZB/W F1 mice[J]. J Immunol, 2017, 199(4): 1238-1249. doi: 10.4049/jimmunol.1700608. DOI URL
[28]	Yamaki S, Ine S, Kawabe T, et al. OX40 and IL-7 play synergistic roles in the homeostatic proliferation of effector memory CD4+ T cells[J]. Eur J Immunol, 2014, 44(10): 3015-3025. doi: 10.1002/eji.201444701. DOI URL
[29]	Jacquemin C, Augusto JF, Scherlinger M, et al. OX40L/OX40 axis impairs follicular and natural Treg function in human SLE[J]. JCI Insight, 2018, 3(24): e122167. doi: 10.1172/jci.insight.122167. DOI
[30]	Marshall A, Celentano A, Cirillo N, et al. Immune receptors CD40 and CD86 in oral keratinocytes and implications for oral lichen planus[J]. J Oral Sci, 2017, 59(3): 373-382. doi: 10.2334/josnusd.16-0334. DOI PMID
[31]	Costa NL, Gonçalves J, De Lima S, et al. Evaluation of PD-L1, PD-L2, PD-1 and cytotoxic immune response in oral lichen planus[J]. Oral Dis, 2020: 13344. doi: 10.1111/odi.13344. DOI
[32]	Zhang J, Tan YQ, Wei MH, et al. TLR4-induced B7-H1 on keratinocytes negatively regulates CD4(+) T cells and CD8(+) T cells responses in oral lichen planus[J]. Exp Dermatol, 2017, 26(5): 409-415. doi: 10.1111/exd.13244. DOI PMID
[33]	Peng Q, Zhang J, Zhou G. Circulating exosomes regulate T-cell-mediated inflammatory response in oral lichen planus[J]. J Oral Pathol Med, 2019, 48(2): 143-150. doi: 10.1111/jop.12804. DOI URL