Research progress of PI3K/AKT/mTOR signaling pathway in pathogenesis of
autoimmune diseases

doi:10.3760/cma.j.issn.1007-1245.2022.15.004

International Medicine and Health Guidance News ›› 2022, Vol. 28 ›› Issue (15): 2089-2093.DOI: 10.3760/cma.j.issn.1007-1245.2022.15.004

• Scientific Research • Previous Articles Next Articles

Research progress of PI3K/AKT/mTOR signaling pathway in pathogenesis of autoimmune diseases

He Chengyan¹, Ma Lei², Xue Haibo¹

¹Department of Endocrinology, Binzhou Medical University Hospital, Binzhou 256603, China; ²Department of Dermatology, Binzhou Medical University Hospital, Binzhou 256603, China

Received:2022-04-24 Online:2022-08-01 Published:2022-08-01
Contact: Xue Haibo, Email: xuehaibo@sina.com
Supported by:
National Natural Science Foundation (81803145);

Innovation Program of Post-graduate Education of Shandong Province (20038612);

Scientific Research and Innovation Team Project of Binzhou Medical University Hospital (202030);

Reserved Leading Talent Project of Binzhou Medical University Hospital (JC2019-03)

PI3K/AKT/mTOR信号通路参与自身免疫性

何呈燕¹ 马蕾² 薛海波¹

¹滨州医学院附属医院内分泌科，滨州　256603； ²滨州医学院附属医院皮肤科，滨州　256603

通讯作者: 薛海波，Email：xuehaibo@sina.com
基金资助:
国家自然科学基金（81803145）；

山东省研究生教育创新计划项目（20038612）；

滨州医学院附属医院科研创新团队项目（202030）；

滨州医学院附属医院后备领军人才项目（JC2019-03）

Abstract

Abstract: Autoimmune diseases (ADs) are a kind of diseases caused by the disorder of immune tolerance and the immune response to autoimmune antigens. Recent studies have found that there are close relationship between the phosphatidylinositol-3-kinase/protein kinase B/target of rapamycin (PI3K/AKT/mTOR) signaling pathway and AD, mainly involved in immune cell proliferation and differentiation, inflammatory cytokine secretion, autophagy levels, and abnormal oxidative stress. This review focuses on the research progress of PI3K/AKT/mTOR signaling pathway in the pathogenesis of AD.

Key words: PI3K, AKT, mTOR, Autoimmune diseases

摘要： 自身免疫性疾病（autoimmune disease，AD）是机体因自身抗原免疫耐受障碍而对自身抗原产生免疫反应，从而引起机体组织损伤的一类疾病。近年研究发现，磷脂酰肌醇-3-激酶/蛋白激酶B/雷帕霉素靶蛋白（phosphatidylin ositol 3-kinase/protein kinase B/mechanistic target of rapamycin kinase，PI3K/AKT/mTOR）信号通路与AD发病密切相关，其主要参与免疫细胞增殖分化、炎性细胞因子分泌、自噬及氧化应激等过程。本文重点概述PI3K/AKT/mTOR信号通路参与AD发病机理的研究进展。

关键词: PI3K, AKT, mTOR, 自身免疫性疾病

He Chengyan, Ma Lei, Xue Haibo. Research progress of PI3K/AKT/mTOR signaling pathway in pathogenesis of autoimmune diseases[J]. International Medicine and Health Guidance News, 2022, 28(15): 2089-2093.

何呈燕　马蕾　薛海波. PI3K/AKT/mTOR信号通路参与自身免疫性[J]. 国际医药卫生导报, 2022, 28(15): 2089-2093.

References

[1] Yu L, Wei J, Liu P. Attacking the PI3K/Akt/mTOR signaling pathway for targeted therapeutic treatment in human cancer[J]. Semin Cancer Biol, 2021,25:S1044-579X(21)00188-7. DOI: 10.1016/j.semcancer.2021.06.019.
[2] Xiao ZX, Miller JS, Zheng SG. An updated advance of autoantibodies in autoimmune diseases[J]. Autoimmun Rev, 2021,20(2):102743. DOI: 10.1016/j.autrev.2020. 102743.
[3] Manning BD, Toker A. AKT/PKB signaling: navigating the network[J]. Cell, 2017,169(3):381-405. DOI: 10.1016/j.cell.2017.04.001.
[4] Buerger C. Epidermal mTORC1 signaling contributes to the pathogenesis of psoriasis and could serve as a therapeutic target[J]. Front Immunol, 2018,9:2786. DOI: 10.3389/fimmu.2018.02786.
[5] Suto T, Karonitsch T. The immunobiology of mTOR in autoimmunity[J]. J Autoimmun, 2020,110:102373. DOI: 10.1016/j.jaut.2019.102373.
[6] Yin Y, Hua H, Li M, et al. mTORC2 promotes type I insulin-like growth factor receptor and insulin receptor activation through the tyrosine kinase activity of mTOR[J]. Cell Res, 2016,26(1):46-65. DOI: 10.1038/cr.2015.133.
[7] Hua H, Kong Q, Zhang H, et al. Targeting mTOR for cancer therapy[J]. J Hematol Oncol, 2019,12(1):71. DOI: 10.1186/s13045-019-0754-1.
[8] Zhao LD, Liang D, Wu XN, et al. Contribution and underlying mechanisms of CXCR4 overexpression in patients with systemic lupus erythematosus[J]. Cell Mol Immunol, 2017,14(10):842-849. DOI: 10.1038/cmi.2016.47.
[9] Long D, Chen Y, Wu H, et al. Clinical significance and immunobiology of IL-21 in autoimmunity[J]. J Autoimmun, 2019,99:1-14. DOI: 10.1016/j.jaut.2019.01.013.
[10] Kurebayashi Y, Nagai S, Ikejiri A, et al. PI3K-Akt-mTORC1-S6K1/2 axis controls Th17 differentiation by regulating Gfi1 expression and nuclear translocation of RORγ[J]. Cell Rep, 2012,1(4):360-373. DOI: 10.1016/j.celrep.2012.02.007.
[11] Wei S, Xie S, Yang Z, et al. Allogeneic adipose-derived stem cells suppress mTORC1 pathway in a murine model of systemic lupus erythematosus[J]. Lupus, 2019,28(2):199-209. DOI: 10.1177/0961203318819131.
[12] Möckel T, Basta F, Weinmann-Menke J, et al. B cell activating factor (BAFF): structure, functions, autoimmunity and clinical implications in systemic lupus Erythematosus (SLE)[J]. Autoimmun Rev, 2021,20(2):102736. DOI: 10.1016/j.autrev.2020.102736.
[13] Ge F, Wang F, Yan X, et al. Association of BAFF with PI3K/Akt/mTOR signaling in lupus nephritis[J]. Mol Med Rep, 2017,16(5):5793-5798. DOI: 10.3892/mmr.2017.7367.
[14] Miura Y, Morooka M, Sax N, et al. Bach2 promotes B cell receptor-induced proliferation of B lymphocytes and represses cyclin-dependent kinase inhibitors[J]. J Immunol, 2018,200(8):2882-2893. DOI: 10.4049/jimmunol.1601863.
[15] Zhu Z, Yang C, Wen L, et al. Bach2 regulates aberrant activation of B cell in systemic lupus erythematosus and can be negatively regulated by BCR-ABL/PI3K[J]. Exp Cell Res, 2018,365(1):138-144. DOI: 10.1016/j.yexcr. 2018. 02.034.
[16] Wang J, Xie L, Wang S, et al. Azithromycin promotes alternatively activated macrophage phenotype in systematic lupus erythematosus via PI3K/Akt signaling pathway[J]. Cell Death Dis, 2018,9(11):1080. DOI: 10. 1038/s41419-018-1097-5.
[17] 薛如君,叶瑞贤,周欣,等.银屑病光疗的应用及疗效[J].国际医药卫生导报,2022,28(5):598-602.DOI:10.3760/cma.j.issn.1007-1245.2022.05.002.
[18] Tu Z, Zhang S, Zhou G, et al. LMO4 is a disease-provocative transcription coregulator activated by IL-23 in psoriatic keratinocytes[J]. J Invest Dermatol, 2018,138(5):1078-1087. DOI: 10.1016/j.jid.2017.12.010.
[19] Varshney P, Saini N. PI3K/AKT/mTOR activation and autophagy inhibition plays a key role in increased cholesterol during IL-17A mediated inflammatory response in psoriasis[J]. Biochim Biophys Acta Mol Basis Dis, 2018,1864 5 Pt A:1795-1803. DOI: 10.1016/j.bbadis. 2018.02.003.
[20] Tang ZL, Zhang K, Lv SC, et al. LncRNA MEG3 suppresses PI3K/AKT/mTOR signalling pathway to enhance autophagy and inhibit inflammation in TNF-α-treated keratinocytes and psoriatic mice[J]. Cytokine, 2021,148:155657. DOI: 10.1016/j.cyto.2021.155657.
[21] Mitra A, Raychaudhuri SK, Raychaudhuri SP. IL-22 induced cell proliferation is regulated by PI3K/Akt/mTOR signaling cascade[J]. Cytokine, 2012,60(1):38-42. DOI: 10.1016/j.cyto.2012.06.316.
[22] Rongna A, Yu P, Hao S, et al. MiR-876-5p suppresses cell proliferation by targeting Angiopoietin-1 in the psoriasis[J]. Biomed Pharmacother, 2018,103:1163-1169. DOI: 10.1016/j.biopha.2018.04.145.
[23] van de Laar L, van den Bosch A, Boonstra A, et al. PI3K-PKB hyperactivation augments human plasmacytoid dendritic cell development and function[J]. Blood, 2012,120(25):4982-4991. DOI: 10.1182/blood-2012-02-413229.
[24] Cao W, Manicassamy S, Tang H, et al. Toll-like receptor-mediated induction of type I interferon in plasmacytoid dendritic cells requires the rapamycin-sensitive PI(3)K-mTOR-p70S6K pathway[J]. Nat Immunol, 2008,9(10):1157-1164. DOI: 10.1038/ni.1645.
[25] Huang T, Lin X, Meng X, et al. Phosphoinositide-3 kinase/protein kinase-B/mammalian target of rapamycin pathway in psoriasis pathogenesis. A potential therapeutic target?[J] Acta Derm Venereol, 2014,94(4):371-379. DOI: 10.2340/00015555-1737.
[26] Lin J, He Y, Wang B, et al. Blocking of YY1 reduce neutrophil infiltration by inhibiting IL-8 production via the PI3K-Akt-mTOR signaling pathway in rheumatoid arthritis[J]. Clin Exp Immunol, 2019,195(2):226-236. DOI: 10.1111/cei.13218.
[27] Qu Y, Zhang YP, Wu J, et al. Downregulated microRNA-135a ameliorates rheumatoid arthritis by inactivation of the phosphatidylinositol 3-kinase/AKT signaling pathway via phosphatidylinositol 3-kinase regulatory subunit 2[J]. J Cell Physiol, 2019,234(10):17663-17676. DOI: 10.1002/jcp.28390.
[28] Wang X, Gong S, Pu D, et al. Up-regulation of miR-365 promotes the apoptosis and restrains proliferation of synoviocytes through downregulation of IGF1 and the inactivation of the PI3K/AKT/mTOR pathway in mice with rheumatoid arthritis[J]. Int Immunopharmacol, 2020,79:106067. DOI: 10.1016/j.intimp.2019.106067.
[29] Huang Z, Xing S, Liu M, et al. MiR-26a-5p enhances cells proliferation, invasion, and apoptosis resistance of fibroblast-like synoviocytes in rheumatoid arthritis by regulating PTEN/PI3K/AKT pathway[J]. Biosci Rep, 2019,39(7):BSR20182192. DOI: 10.1042/BSR20182192.
[30] Li S, Chen JW, Xie X, et al. Autophagy inhibitor regulates apoptosis and proliferation of synovial fibroblasts through the inhibition of PI3K/AKT pathway in collagen-induced arthritis rat model[J]. Am J Transl Res, 2017,9(5):2065-2076.
[31] Lai K, Zhang W, Li S, et al. mTOR pathway regulates the differentiation of peripheral blood Th2/Treg cell subsets in patients with pemphigus vulgaris[J]. Acta Biochim Biophys Sin (Shanghai), 2021,53(4):438-445. DOI: 10.1093/abbs/gmab008.
[32] Zeng P, Liu W, Yang X, et al. Qing Zao Fang (QZF) alleviates the inflammatory microenvironment of the submandibular gland in Sjögren's syndrome based on the PI3K/Akt/HIF-1α/VEGF signaling pathway[J]. Dis Markers, 2022,2022:6153459. DOI: 10.1155/2022/6153459.
[33] Wang J, Wang X, Wang L, et al. MiR-let-7d-3p regulates IL-17 expression through targeting AKT1/mTOR signaling in CD4+ T cells[J]. In Vitro Cell Dev Biol Anim, 2020,56(1):67-74. DOI: 10.1007/s11626-019-00409-5.

Research progress of PI3K/AKT/mTOR signaling pathway in pathogenesis of autoimmune diseases

PI3K/AKT/mTOR信号通路参与自身免疫性

Knowledge

Abstract

Cite this article

share this article

References

Related Articles 3

Recommended Articles

Metrics

[1]	Xing Xiaoyun, Ma Lei. Research progress of PI3K/AKT signaling pathway in pathogenesis of psoriasis [J]. International Medicine and Health Guidance News, 2022, 28(5): 594-597.
[2]	Xiong Yanlin, Xie Lina, Qi Liuying. Chlorogenic acid inhibits apoptosis of human periodontal ligament cells in high glucose environment via AKT signaling pathway [J]. International Medicine and Health Guidance News, 2022, 28(1): 96-99.
[3]	Wu Jianmin, Jia Xiuhong, Zhang Jian. PI3K/AKT signaling pathway and leukemia [J]. International Medicine and Health Guidance News, 2021, 27(6): 795-798.