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REVIEW ARTICLE

New insight in treating autoimmune diseases by targeting autophagy

, , & ORCID Icon
Article: 2351872 | Received 22 Jan 2024, Accepted 28 Apr 2024, Published online: 13 May 2024

References

  • Deter RL, De Duve C. Influence of glucagon, an inducer of cellular autophagy, on some physical properties of rat liver lysosomes. J Cell Biol. 1967;33(2):1–22.
  • Boya P, Reggiori F, Codogno P. Emerging regulation and functions of autophagy. Nat Cell Biol. 2013;15(7):713–720.
  • Levine B, Kroemer G. Biological functions of autophagy genes: a disease perspective. Cell. 2019;176(1–2):11–42.
  • Deretic V, Saitoh T, Akira S. Autophagy in infection, inflammation and immunity. Nat Rev Immunol. 2013;13(10):722–737.
  • Nakatogawa H. Mechanisms governing autophagosome biogenesis. Nat Rev Mol Cell Biol. 2020;21(8):439–458.
  • Vargas JNS, Hamasaki M, Kawabata T, et al. The mechanisms and roles of selective autophagy in mammals. Nat Rev Mol Cell Biol. 2023;24(3):167–185.
  • Turco E, Witt M, Abert C, et al. FIP200 claw domain binding to p62 promotes autophagosome formation at ubiquitin condensates. Mol Cell. 2019;74(2):330–346.
  • Pan M, Yin Y, Hu T, et al. UXT attenuates the CGAS-STING1 signaling by targeting STING1 for autophagic degradation. Autophagy. 2023;19(2):440–456.
  • Vargas JNS, Wang C, Bunker E, et al. Spatiotemporal control of ULK1 activation by NDP52 and TBK1 during selective autophagy. Mol Cell. 2019;74(2):347–362.
  • Kaushik S, Cuervo AM. The coming of age of chaperone-mediated autophagy. Nat Rev Mol Cell Biol. 2018;19(6):365–381.
  • Qiao L, Ma J, Zhang Z, et al. Deficient chaperone-mediated autophagy promotes inflammation and atherosclerosis. Circ Res. 2021;129(12):1141–1157.
  • Madrigal-Matute J, Cuervo AM, Sluimer JC. Chaperone-mediated autophagy protects against atherosclerosis. Autophagy. 2022;18(10):2505–2507.
  • Kaushik S, Juste YR, Lindenau K, et al. Chaperone-mediated autophagy regulates adipocyte differentiation. Sci Adv. 2022;8(46):eabq2733.
  • Bourdenx M, Martín-Segura A, Scrivo A, et al. Chaperone-mediated autophagy prevents collapse of the neuronal metastable proteome. Cell. 2021;184(10):2696–2714.
  • Dong S, Wang Q, Kao YR, et al. Chaperone-mediated autophagy sustains haematopoietic stem-cell function. Nature. 2021;591(7848):117–123.
  • Fan Y, Hou T, Gao Y, et al. Acetylation-dependent regulation of TPD52 isoform 1 modulates chaperone-mediated autophagy in prostate cancer. Autophagy. 2021;17(12):4386–4400.
  • Wang L, Klionsky DJ, Shen HM. The emerging mechanisms and functions of microautophagy. Nat Rev Mol Cell Biol. 2023;24(3):186–203.
  • Kuchitsu Y, Mukai K, Uematsu R, et al. STING signalling is terminated through ESCRT-dependent microautophagy of vesicles originating from recycling endosomes. Nat Cell Biol. 2023;25(3):453–466.
  • Mizushima N, Yoshimori T, Ohsumi Y. The role of atg proteins in autophagosome formation. Annu Rev Cell Dev Biol. 2011;27(1):107–132.
  • Li Z, Zhang X. Phospho-regulation and function of ULK1-ATG13 during the cell cycle. Autophagy. 2021;17(4):1054–1056.
  • Mauthe M, Reggiori F. ATG proteins: are we always looking at autophagy? Autophagy. 2016;12(12):2502–2503.
  • Guo W, Wang Q, Pan S, et al. The ERK1/2-ATG13-FIP200 signaling Cascade is required for autophagy induction to protect renal cells from hypoglycemia-induced cell death. J Cell Physiol. 2021;236(10):6932–6947.
  • Ning J, Pei Z, Wang M, et al. Site-specific Atg13 methylation-mediated autophagy regulates epithelial inflammation in PM2.5-induced pulmonary fibrosis. J Hazard Mater. 2023;457:131791.
  • Yang Y, Zhu Y, Zhou S, et al. TRIM27 cooperates with STK38L to inhibit ULK1-mediated autophagy and promote tumorigenesis. Embo J. 2022;41(14):e109777.
  • Choi HMC, Li Y, Suraj D, et al. Autophagy protein ULK1 interacts with and regulates SARM1 during axonal injury. Proc Natl Acad Sci USA. 2022;119(47):e2203824119.
  • Ma Z, Li L, Livingston MJ, et al. p53/microRNA-214/ULK1 axis impairs renal tubular autophagy in diabetic kidney disease. J Clin Invest. 2020;130(9):5011–5026.
  • Li GM, Li L, Li MQ, et al. DAPK3 inhibits gastric cancer progression via activation of ULK1-dependent autophagy. Cell Death Differ. 2021;28(3):952–967.
  • Guardia CM, Tan XF, Lian T, et al. Structure of human ATG9A, the only transmembrane protein of the core autophagy machinery. Cell Rep. 2020;31(13):107837.
  • Yamamoto H, Kakuta S, Watanabe TM, et al. Atg9 vesicles are an important membrane source during early steps of autophagosome formation. J Cell Biol. 2012;198(2):219–233.
  • Mari M, Griffith J, Rieter E, et al. An Atg9-containing compartment that functions in the early steps of autophagosome biogenesis. J Cell Biol. 2010;190(6):1005–1022.
  • Osawa T, Kotani T, Kawaoka T, et al. Atg2 mediates direct lipid transfer between membranes for autophagosome formation. Nat Struct Mol Biol. 2019;26(4):281–288.
  • Maeda S, Otomo C, Otomo T. The autophagic membrane tether ATG2A transfers lipids between membranes. Elife. 2019;8:e45777.
  • Matoba K, Kotani T, Tsutsumi A, et al. Atg9 is a lipid scramblase that mediates autophagosomal membrane expansion. Nat Struct Mol Biol. 2020;27(12):1185–1193.
  • Sawa-Makarska J, Baumann V, Coudevylle N, et al. Reconstitution of autophagosome nucleation defines Atg9 vesicles as seeds for membrane formation. Science. 2020;369(6508):eaaz7714.
  • Mercer TJ, Gubas A, Tooze SA. A molecular perspective of mammalian autophagosome biogenesis. J Biol Chem. 2018;293(15):5386–5395.
  • Vicinanza M, Korolchuk VI, Ashkenazi A, et al. PI(5)P regulates autophagosome biogenesis. Mol Cell. 2015;57(2):219–234.
  • Yang G, Song W, Postoak JL, et al. Autophagy-related protein PIK3C3/VPS34 controls T cell metabolism and function. Autophagy. 2021;17(5):1193–1204.
  • Yang G, Postoak JL, Song W, et al. Dendritic cell PIK3C3/VPS34 controls the pathogenicity of CNS autoimmunity independently of LC3-associated phagocytosis. Autophagy. 2022;18(1):161–170.
  • Lv Y, Zhang W, Zhao J, et al. SRSF1 inhibits autophagy through regulating bcl-x splicing and interacting with PIK3C3 in lung cancer. Signal Transduct Target Ther. 2021;6(1):108.
  • Johansen T, Lamark T. Selective autophagy: ATG8 family proteins, LIR motifs and cargo receptors. J Mol Biol. 2020;432(1):80–103.
  • Tanida I, Ueno T, Kominami E. LC3 conjugation system in mammalian autophagy. Int J Biochem Cell Biol. 2004;36(12):2503–2518.
  • Fujita N, Itoh T, Omori H, et al. The Atg16L complex specifies the site of LC3 lipidation for membrane biogenesis in autophagy. Mol Biol Cell. 2008;19(5):2092–2100.
  • Koyama-Honda I, Itakura E, Fujiwara TK, et al. Temporal analysis of recruitment of mammalian ATG proteins to the autophagosome formation site. Autophagy. 2013;9(10):1491–1499.
  • Yu ZQ, Ni T, Hong B, et al. Dual roles of Atg8-PE deconjugation by Atg4 in autophagy. Autophagy. 2012;8(6):883–892.
  • Jounai N, Takeshita F, Kobiyama K, et al. The Atg5 Atg12 conjugate associates with innate antiviral immune responses. Proc Natl Acad Sci USA. 2007;104(35):14050–14055.
  • Peng X, Wang Y, Li H, et al. ATG5-mediated autophagy suppresses NF-κB signaling to limit epithelial inflammatory response to kidney injury. Cell Death Dis. 2019;10(4):253.
  • Oh DS, Lee HK. Autophagy protein ATG5 regulates CD36 expression and anti-tumor MHC class II antigen presentation in dendritic cells. Autophagy. 2019;15(12):2091–2106.
  • Zhang L, Chen X, Chang M, et al. MiR-30c-5p/ATG5 axis regulates the progression of Parkinson’s disease. Front Cell Neurosci. 2021;15:644507.
  • Durgan J, Lystad AH, Sloan K, et al. Non-canonical autophagy drives alternative ATG8 conjugation to phosphatidylserine. Mol Cell. 2021;81(9):2031–2040.
  • Schreiber A, Collins BC, Davis C, et al. Multilayered regulation of autophagy by the Atg1 kinase orchestrates spatial and temporal control of autophagosome formation. Mol Cell. 2021;81(24):5066–5081.
  • Pisetsky DS. Pathogenesis of autoimmune disease. Nat Rev Nephrol. 2023;19(8):509–524.
  • Wang L, Wang FS, Gershwin ME. Human autoimmune diseases: a comprehensive update. J Intern Med. 2015;278(4):369–395.
  • Aslani S, Mahmoudi M, Karami J, et al. Epigenetic alterations underlying autoimmune diseases. Autoimmunity. 2016;49(2):69–83.
  • Gianchecchi E, Delfino DV, Fierabracci A. Recent insights on the putative role of autophagy in autoimmune diseases. Autoimmun Rev. 2014;13(3):231–241.
  • Zhang M, Yao C, Cai J, et al. LRRK2 is involved in the pathogenesis of system lupus erythematosus through promoting pathogenic antibody production. J Transl Med. 2019;17(1):37.
  • Kato H, Perl A. Blockade of treg cell differentiation and function by the interleukin-21-Mechanistic target of rapamycin axis via suppression of autophagy in patients with systemic lupus erythematosus. Arthritis Rheumatol. 2018;70(3):427–438.
  • van Loosdregt J, Rossetti M, Spreafico R, et al. Increased autophagy in CD4(+) T cells of rheumatoid arthritis patients results in T-cell hyperactivation and apoptosis resistance. Eur J Immunol. 2016;46(12):2862–2870.
  • Lee WS, Kato M, Sugawara E, et al. Protective role of optineurin against joint destruction in rheumatoid arthritis synovial fibroblasts. Arthritis Rheumatol. 2020;72(9):1493–1504.
  • Fernandes MGF, Mohammadnia A, Pernin F, et al. Mechanisms of metabolic stress induced cell death of human oligodendrocytes: relevance for progressive multiple sclerosis. Acta Neuropathol Commun. 2023;11(1):108.
  • Berglund R, Guerreiro-Cacais AO, Adzemovic MZ, et al. Microglial autophagy-associated phagocytosis is essential for recovery from neuroinflammation. Sci Immunol. 2020;5(52):eabb5077.
  • Mehto S, Jena KK, Nath P, et al. The Crohn’s disease risk factor IRGM limits NLRP3 inflammasome activation by impeding its assembly and by mediating its selective autophagy. Mol Cell. 2019;73(3):429–445.
  • Nighot PK, Hu CA, Ma TY. Autophagy enhances intestinal epithelial tight junction barrier function by targeting claudin-2 protein degradation. J Biol Chem. 2015;290(11):7234–7246.
  • Deretic V. Autophagy in inflammation, infection, and immunometabolism. Immunity. 2021;54(3):437–453.
  • Chen H, Liu H, Lu C, et al. PSORI-CM02 formula increases CD4+ Foxp3+ regulatory T cell frequency and ameliorates imiquimod-induced psoriasis in mice. Front Immunol. 2017;8:1767.
  • Yue L, Ailin W, Jinwei Z, et al. PSORI-CM02 ameliorates psoriasis in vivo and in vitro by inducing autophagy via inhibition of the PI3K/akt/mTOR pathway. Phytomedicine. 2019;64:153054.
  • Wang W, Xu D, Huang Y, et al. Identification of the role of autophagy-related TNFSF10/hsa-let-7a-5p axis in vitiligo development and potential herbs exploring based on a bioinformatics analysis. Heliyon. 2023;9(12):e23220.
  • Cui T, Wang Y, Song P, et al. HSF1-Dependent autophagy activation contributes to the survival of melanocytes under oxidative stress in vitiligo. J Invest Dermatol. 2022;142(6):1659–1669.
  • Macri C, Wang F, Tasset I, et al. Modulation of deregulated chaperone-mediated autophagy by a phosphopeptide. Autophagy. 2015;11(3):472–486.
  • Qi YY, Zhou XJ, Nath SK, et al. A rare variant (rs933717) at FBXO31-MAP1LC3B in Chinese is associated with systemic lupus erythematosus. Arthritis Rheumatol. 2018;70(2):287–297.
  • Bockus LB, Matsuzaki S, Vadvalkar SS, et al. Cardiac insulin signaling regulates glycolysis through phosphofructokinase 2 content and activity. J Am Heart Assoc. 2017;6(12):e007159.
  • Kiriakidou M, Ching CL. Systemic lupus erythematosus. Ann Intern Med. 2020;172(11):Itc81–itc96.
  • Muhammad Yusoff F, Wong KK, Mohd Redzwan N. Th1, Th2, and Th17 cytokines in systemic lupus erythematosus. Autoimmunity. 2020;53(1):8–20.
  • Ceccarelli F, Perricone C, Natalucci F, et al. Organ damage in systemic lupus erythematosus patients: a multifactorial phenomenon. Autoimmun Rev. 2023;22(8):103374.
  • Ameer MA, Chaudhry H, Mushtaq J, et al. An overview of systemic lupus erythematosus (SLE) pathogenesis, classification, and management. Cureus. 2022;14(10):e30330.
  • Owen KA, Grammer AC, Lipsky PE. Deconvoluting the heterogeneity of SLE: the contribution of ancestry. J Allergy Clin Immunol. 2022;149(1):12–23.
  • Grosjean I, Roméo B, Domdom MA, et al. Autophagopathies: from autophagy gene polymorphisms to precision medicine for human diseases. Autophagy. 2022;18(11):2519–2536.
  • Qi YY, Zhou XJ, Zhang H. Autophagy and immunological aberrations in systemic lupus erythematosus. Eur J Immunol. 2019;49(4):523–533.
  • López P, Alonso-Pérez E, Rodríguez-Carrio J, et al. Influence of Atg5 mutation in SLE depends on functional IL-10 genotype. PLoS One. 2013;8(10):e78756.
  • Zhou XJ, Lu XL, Lv JC, et al. Genetic association of PRDM1-ATG5 intergenic region and autophagy with systemic lupus erythematosus in a Chinese population. Ann Rheum Dis. 2011;70(7):1330–1337.
  • Arbogast F, Arnold J, Hammann P, et al. ATG5 is required for B cell polarization and presentation of particulate antigens. Autophagy. 2019;15(2):280–294.
  • Clarke AJ, Ellinghaus U, Cortini A, et al. Autophagy is activated in systemic lupus erythematosus and required for plasmablast development. Ann Rheum Dis. 2015;74(5):912–920.
  • Ishibashi K, Fujita N, Kanno E, et al. Atg16L2, a novel isoform of mammalian Atg16L that is not essential for canonical autophagy despite forming an Atg12–5-16L2 complex. Autophagy. 2011;7(12):1500–1513.
  • Wible DJ, Chao HP, Tang DG, et al. ATG5 cancer mutations and alternative mRNA splicing reveal a conjugation switch that regulates ATG12-ATG5-ATG16L1 complex assembly and autophagy. Cell Discov. 2019;5(1):42.
  • Don Wai Luu L, Kaakoush NO, Castaño-Rodríguez N. The role of ATG16L2 in autophagy and disease. Autophagy. 2022;18(11):2537–2546.
  • Singh B, Maiti GP, Zhou X, et al. Lupus susceptibility region containing CDKN1B rs34330 mechanistically influences expression and function of multiple target genes, also linked to proliferation and apoptosis. Arthritis Rheumatol. 2021;73(12):2303–2313.
  • Chung CP, Karakoc G, Dickson A, et al. APOL1 and the risk of adverse renal outcomes in patients of african ancestry with systemic lupus erythematosus. Lupus. 2023;32(6):763–770.
  • Blazer AD, Clancy RM. ApoL1 and the immune response of patients with systemic lupus erythematosus. Curr Rheumatol Rep. 2017;19(3):13.
  • Raza IGA, Clarke AJ. B cell metabolism and autophagy in autoimmunity. Front Immunol. 2021;12:681105.
  • Weindel CG, Richey LJ, Bolland S, et al. B cell autophagy mediates TLR7-dependent autoimmunity and inflammation. Autophagy. 2015;11(7):1010–1024.
  • Caza TN, Talaber G, Perl A. Metabolic regulation of organelle homeostasis in lupus T cells. Clin Immunol. 2012;144(3):200–213.
  • Caza TN, Fernandez DR, Talaber G, et al. HRES-1/Rab4-mediated depletion of Drp1 impairs mitochondrial homeostasis and represents a target for treatment in SLE. Ann Rheum Dis. 2014;73(10):1888–1897.
  • Chen PM, Katsuyama E, Satyam A, et al. CD38 reduces mitochondrial fitness and cytotoxic T cell response against viral infection in lupus patients by suppressing mitophagy. Sci Adv. 2022;8(24):eabo4271.
  • Frangou E, Chrysanthopoulou A, Mitsios A, et al. REDD1/autophagy pathway promotes thromboinflammation and fibrosis in human systemic lupus erythematosus (SLE) through NETs decorated with tissue factor (TF) and interleukin-17A (IL-17A). Ann Rheum Dis. 2019;78(2):238–248.
  • Hsieh YT, Chen YC, Chou YC, et al. Long noncoding RNA SNHG16 regulates TLR4-mediated autophagy and NETosis formation in alveolar hemorrhage associated with systemic lupus erythematosus. J Biomed Sci. 2023;30(1):78.
  • Xue Z, Zhang Z, Liu H, et al. lincRNA-Cox2 regulates NLRP3 inflammasome and autophagy mediated neuroinflammation. Cell Death Differ. 2019;26(1):130–145.
  • Wang K, Liu JD, Deng G, et al. LncSIK1 enhanced the sensitivity of AML cells to retinoic acid by the E2F1/autophagy pathway. Cell Prolif. 2022;55(3):e13185.
  • Pan M, Hu T, Lyu J, et al. CSNK1A1/CK1α suppresses autoimmunity by restraining the CGAS-STING1 signaling. Autophagy. 2023;20(2):311–328.
  • Sokolova MV, Schett G, Steffen U. Autoantibodies in rheumatoid arthritis: historical background and novel findings. Clin Rev Allergy Immunol. 2022;63(2):138–151.
  • McGonagle D, Watad A, Savic S. Mechanistic immunological based classification of rheumatoid arthritis. Autoimmun Rev. 2018; Nov17(11):1115–1123.
  • Kim K, Bang SY, Lee HS, et al. Update on the genetic architecture of rheumatoid arthritis. Nat Rev Rheumatol. 2017;13(1):13–24.
  • Zhao J, Jiang P, Guo S, et al. Apoptosis, autophagy, NETosis, necroptosis, and pyroptosis mediated programmed cell death as targets for innovative therapy in rheumatoid arthritis. Front Immunol. 2021;12:809806.
  • Chen YM, Chang CY, Chen HH, et al. Association between autophagy and inflammation in patients with rheumatoid arthritis receiving biologic therapy. Arthritis Res Ther. 2018;20(1):268.
  • Shi J, van Veelen PA, Mahler M, et al. Carbamylation and antibodies against carbamylated proteins in autoimmunity and other pathologies. Autoimmun Rev. 2014;13(3):225–230.
  • Manganelli V, Recalchi S, Capozzi A, et al. Autophagy induces protein carbamylation in fibroblast-like synoviocytes from patients with rheumatoid arthritis. Rheumatology (Oxford). 2018;57(11):2032–2041.
  • Pope RM. Apoptosis as a therapeutic tool in rheumatoid arthritis. Nat Rev Immunol. 2002;2(7):527–535.
  • Xu K, Xu P, Yao JF, et al. Reduced apoptosis correlates with enhanced autophagy in synovial tissues of rheumatoid arthritis. Inflamm Res. 2013;62(2):229–237.
  • Kim EK, Kwon JE, Lee SY, et al. IL-17-mediated mitochondrial dysfunction impairs apoptosis in rheumatoid arthritis synovial fibroblasts through activation of autophagy. Cell Death Dis. 2017;8(1):e2565.
  • Yang Z, Fujii H, Mohan SV, et al. Phosphofructokinase deficiency impairs ATP generation, autophagy, and redox balance in rheumatoid arthritis T cells. J Exp Med. 2013;210(10):2119–2134.
  • Wei W, Ren J, Yin W, et al. Inhibition of CTSK modulates periodontitis with arthritis via downregulation of TLR9 and autophagy. Cell Prolif. 2020;53(1):e12722.
  • Willemsen J, Neuhoff MT, Hoyler T, et al. TNF leads to mtDNA release and cGAS/STING-dependent interferon responses that support inflammatory arthritis. Cell Rep. 2021;37(6):109977.
  • Loh C, Park SH, Lee A, et al. TNF-induced inflammatory genes escape repression in fibroblast-like synoviocytes: transcriptomic and epigenomic analysis. Ann Rheum Dis. 2019;78(9):1205–1214.
  • Yang J, Liu J, Li J, et al. Celastrol inhibits rheumatoid arthritis by inducing autophagy via inhibition of the PI3K/AKT/mTOR signaling pathway. Int Immunopharmacol. 2022;112:109241.
  • He SD, Huang SG, Zhu HJ, et al. Oridonin suppresses autophagy and survival in rheumatoid arthritis fibroblast-like synoviocytes. Pharm Biol. 2020;58(1):146–151.
  • Fernández-Rodríguez JA, Almonte-Becerril M, Ramil-Gómez O, et al. Autophagy activation by resveratrol reduces severity of experimental rheumatoid arthritis. Mol Nutr Food Res. 2021;65(2):e2000377.
  • Fan DD, Tan PY, Jin L, et al. Bioinformatic identification and validation of autophagy-related genes in rheumatoid arthritis. Clin Rheumatol. 2023;42(3):741–750.
  • Huang RZ, Zheng J, Liu FL, et al. A novel autophagy-related marker for improved differential diagnosis of rheumatoid arthritis and osteoarthritis. Front Genet. 2021;12:743560.
  • Cai Y, Xu K, Aihaiti Y, et al. Derlin-1, as a potential early predictive biomarker for nonresponse to infliximab treatment in rheumatoid arthritis, is related to autophagy. Front Immunol. 2021;12:795912.
  • McGinley MP, Goldschmidt CH, Rae-Grant AD. Diagnosis and treatment of multiple sclerosis: a review. Jama. 2021;325(8):765–779.
  • The Lancet N. Multiple sclerosis under the spotlight.Lancet Neurol. 2021;20(7):497.
  • Dobson R, Giovannoni G. Multiple sclerosis - a review. Eur J Neurol. 2019;26(1):27–40.
  • Misrielal C, Mauthe M, Reggiori F, et al. Autophagy in multiple sclerosis: two sides of the same coin. Front Cell Neurosci. 2020;14:603710.
  • Igci M, Baysan M, Yigiter R, et al. Gene expression profiles of autophagy-related genes in multiple sclerosis. Gene. 2016;588(1):38–46.
  • Misrielal C, Alsema AM, Wijering MHC, et al. Transcriptomic changes in autophagy-related genes are inversely correlated with inflammation and are associated with multiple sclerosis lesion pathology. Brain Behav Immun Health. 2022;25:100510.
  • Srimat Kandadai K, Kotur MB, Dokalis N, et al. ATG5 in microglia does not contribute vitally to autoimmune neuroinflammation in mice. Autophagy. 2021;17(11):3566–3576.
  • Li Y, Zhou D, Ren Y, et al. Mir223 restrains autophagy and promotes CNS inflammation by targeting ATG16L1. Autophagy. 2019;15(3):478–492.
  • Patergnani S, Castellazzi M, Bonora M, et al. Autophagy and mitophagy elements are increased in body fluids of multiple sclerosis-affected individuals. J Neurol Neurosurg Psychiatry. 2018;89(4):439–441.
  • Di Rita A, Strappazzon F. A protective variant of the autophagy receptor CALCOCO2/NDP52 in multiple sclerosis (MS). Autophagy. 2021;17(6):1565–1567.
  • de Lange KM, Barrett JC. Understanding inflammatory bowel disease via immunogenetics. J Autoimmun. 2015;64:91–100.
  • Shaw MH, Kamada N, Warner N, et al. The ever-expanding function of NOD2: autophagy, viral recognition, and T cell activation. Trends Immunol. 2011;32(2):73–79.
  • Philpott DJ, Sorbara MT, Robertson SJ, et al. NOD proteins: regulators of inflammation in health and disease. Nat Rev Immunol. 2014;14(1):9–23.
  • Aden K, Tran F, Ito G, et al. ATG16L1 orchestrates interleukin-22 signaling in the intestinal epithelium via cGAS-STING. J Exp Med. 2018;215(11):2868–2886.
  • Larabi A, Barnich N, Nguyen HTT. New insights into the interplay between autophagy, gut microbiota and inflammatory responses in IBD. Autophagy. 2020;16(1):38–51.
  • Wu MY, Liu L, Wang EJ, et al. PI3KC3 complex subunit NRBF2 is required for apoptotic cell clearance to restrict intestinal inflammation. Autophagy. 2021;17(5):1096–1111.
  • Barker N. Adult intestinal stem cells: critical drivers of epithelial homeostasis and regeneration. Nat Rev Mol Cell Biol. 2014;15(1):19–33.
  • Kim S, Lee JY, Shin SG, et al. ESRRA (estrogen related receptor alpha) is a critical regulator of intestinal homeostasis through activation of autophagic flux via gut microbiota. Autophagy. 2021;17(10):2856–2875.
  • Cosin-Roger J, Simmen S, Melhem H, et al. Hypoxia ameliorates intestinal inflammation through NLRP3/mTOR downregulation and autophagy activation. Nat Commun. 2017;8(1):98.
  • Saha K, Subramenium Ganapathy A, Wang A, et al. Autophagy reduces the degradation and promotes membrane localization of occludin to enhance the intestinal epithelial tight junction barrier against paracellular macromolecule flux. J Crohns Colitis. 2023;17(3):433–449.
  • Ganapathy AS, Saha K, Suchanec E, et al. AP2M1 mediates autophagy-induced CLDN2 (claudin 2) degradation through endocytosis and interaction with LC3 and reduces intestinal epithelial tight junction permeability. Autophagy. 2022;18(9):2086–2103.
  • Liu M, Sun T, Li N, et al. BRG1 attenuates colonic inflammation and tumorigenesis through autophagy-dependent oxidative stress sequestration. Nat Commun. 2019;10(1):4614.
  • Griffiths CEM, Armstrong AW, Gudjonsson JE, et al. Psoriasis. Lancet. 2021;397(10281):1301–1315.
  • Griffiths CE, Barker JN. Pathogenesis and clinical features of psoriasis. Lancet. 2007;370(9583):263–271.
  • Klapan K, Frangež Ž, Markov N, et al. Evidence for lysosomal dysfunction within the epidermis in psoriasis and atopic dermatitis. J Invest Dermatol. 2021;141(12):2838–2848.
  • Bai S, Cheng H, Li H, et al. Integrated bioinformatics analysis identifies autophagy-associated genes as candidate biomarkers and reveals the immune infiltration landscape in psoriasis. Autoimmunity. 2024;57(1):2259137.
  • Sánchez-Martín P, Saito T, Komatsu M. p62/SQSTM1: ‘Jack of all trades’ in health and cancer. Febs J. 2019;286(1):8–23.
  • Mahil SK, Twelves S, Farkas K, et al. AP1S3 mutations cause skin autoinflammation by disrupting keratinocyte autophagy and up-regulating IL-36 production. J Invest Dermatol. 2016;136(11):2251–2259.
  • Kim HR, Kang SY, Kim HO, et al. Role of aryl hydrocarbon receptor activation and autophagy in psoriasis-related inflammation. Int J Mol Sci. 2020;21(6):2195.
  • 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. Biochim Biophys Acta Mol Basis Dis. 2018;1864(5 Pt A):1795–1803.
  • Song J, Jiang J, Kuai L, et al. TMT-based proteomics analysis reveals the protective effect of jueyin granules on imiquimod-induced psoriasis mouse model by causing autophagy. Phytomedicine. 2022;96:153846.
  • Ezzedine K, Eleftheriadou V, Whitton M, et al. Vitiligo. Lancet. 2015;386(9988):74–84.
  • Frisoli ML, Essien K, Harris JE. Vitiligo: mechanisms of pathogenesis and treatment. Annu Rev Immunol. 2020;38(1):621–648.
  • Bastonini E, Kovacs D, Raffa S, et al. A protective role for autophagy in vitiligo. Cell Death Dis. 2021;12(4):318.
  • Yang Y, Wu X, Lu X, et al. Identification and validation of autophagy-related genes in vitiligo. Cells. 2022;11(7):1116.
  • Kang P, Wang Y, Chen J, et al. TRPM2-dependent autophagy inhibition exacerbates oxidative stress-induced CXCL16 secretion by keratinocytes in vitiligo. J Pathol. 2024;262(4):441–453.
  • Fan X, Men R, Huang C, et al. Critical roles of conventional dendritic cells in autoimmune hepatitis via autophagy regulation. Cell Death Dis. 2020;11(1):23.
  • Muralidharan C, Conteh AM, Marasco MR, et al. Pancreatic beta cell autophagy is impaired in type 1 diabetes. Diabetologia. 2021;64(4):865–877.
  • Muralidharan C, Linnemann AK. β-cell autophagy in the pathogenesis of type 1 diabetes. Am J Physiol Endocrinol Metab. 2021;321(3):e410–e416.
  • Wang H, Wang L, Hu F, et al. Neuregulin-4 attenuates diabetic cardiomyopathy by regulating autophagy via the AMPK/mTOR signalling pathway. Cardiovasc Diabetol. 2022;21(1):205.
  • Schuster C, Gerold KD, Schober K, et al. The autoimmunity-associated gene CLEC16A modulates thymic epithelial cell autophagy and alters T cell selection. Immunity. 2015;42(5):942–952.
  • Rangel M, Kong J, Bhatt V, et al. Autophagy and tumorigenesis. Febs J. 2022;289(22):7177–7198.
  • Yu S, Wang Y, Jing L, et al. Autophagy in the “inflammation-carcinogenesis” pathway of liver and HCC immunotherapy. Cancer Lett. 2017;411:82–89.
  • Lei Y, Xu X, Liu H, et al. HBx induces hepatocellular carcinogenesis through ARRB1-mediated autophagy to drive the G(1)/S cycle. Autophagy. 2021;17(12):4423–4441.
  • Görgülü K, Diakopoulos KN, Ai J, et al. Levels of the autophagy-related 5 protein affect progression and metastasis of pancreatic tumors in mice. Gastroenterology. 2019;156(1):203–217.
  • Keulers TG, Koch A, van Gisbergen MW, et al. ATG12 deficiency results in intracellular glutamine depletion, abrogation of tumor hypoxia and a favorable prognosis in cancer. Autophagy. 2022;18(8):1898–1914.
  • Masutani M, Nakagama H, Sugimura T. Poly(ADP-ribosyl)ation in relation to cancer and autoimmune disease. Cell Mol Life Sci. 2005;62(7–8):769–783.
  • Levine B, Mizushima N, Virgin HW. Autophagy in immunity and inflammation. Nature. 2011;469(7330):323–335.
  • Bonam SR, Wang F, Muller S. Autophagy: a new concept in autoimmunity regulation and a novel therapeutic option. J Autoimmun. 2018;94:16–32.
  • Schrezenmeier E, Dörner T. Mechanisms of action of hydroxychloroquine and chloroquine: implications for rheumatology. Nat Rev Rheumatol. 2020;16(3):155–166.
  • Wu SF, Chang CB, Hsu JM, et al. Hydroxychloroquine inhibits CD154 expression in CD4(+) T lymphocytes of systemic lupus erythematosus through NFAT, but not STAT5, signaling. Arthritis Res Ther. 2017;19(1):183.
  • Yang G, Van Kaer L. Therapeutic targeting of immune cell autophagy in multiple sclerosis: russian roulette or silver bullet? Front Immunol. 2021;12:724108.
  • Prabakaran T, Troldborg A, Kumpunya S, et al. A STING antagonist modulating the interaction with STIM1 blocks ER-to-golgi trafficking and inhibits lupus pathology. EBioMedicine. 2021;66:103314.
  • Hsu HC, Chen YH, Lin TS, et al. Systemic lupus erythematosus is associated with impaired autophagic degradation via interleukin-6 in macrophages. Biochim Biophys Acta Mol Basis Dis. 2021;1867(2):166027.
  • Zhao XY, Li SS, He YX, et al. SGLT2 inhibitors alleviated podocyte damage in lupus nephritis by decreasing inflammation and enhancing autophagy. Ann Rheum Dis. 2023;82(10):1328–1340.
  • Page N, Gros F, Schall N, et al. A therapeutic peptide in lupus alters autophagic processes and stability of MHCII molecules in MRL/lpr B cells. Autophagy. 2011;7(5):539–540.
  • Wilhelm M, Wang F, Schall N, et al. Lupus regulator peptide P140 represses B cell differentiation by reducing HLA class II molecule overexpression. Arthritis Rheumatol. 2018;70(7):1077–1088.
  • Retnakumar SV, Geesala R, Bretin A, et al. Targeting the endo-lysosomal autophagy pathway to treat inflammatory bowel diseases. J Autoimmun. 2022;128:102814.
  • Yuan K, Zhu Q, Lu Q, et al. Quercetin alleviates rheumatoid arthritis by inhibiting neutrophil inflammatory activities. J Nutr Biochem. 2020;84:108454.
  • Cai J, Zhang LC, Zhao RJ, et al. Chelerythrine ameliorates rheumatoid arthritis by modulating the AMPK/mTOR/ULK-1 signaling pathway. Phytomedicine. 2022;104:154140.bMed PMID: 35752081; eng.
  • Sandborn WJ, Feagan BG, Marano C, et al. Subcutaneous golimumab maintains clinical response in patients with moderate-to-severe ulcerative colitis. Gastroenterology. 2014;146(1):96–109.
  • Lee YS, Gupta DP, Park SH, et al. Anti-inflammatory effects of dimethyl fumarate in microglia via an autophagy dependent pathway. Front Pharmacol. 2021;12:612981.
  • Patergnani S, Bonora M, Ingusci S, et al. Antipsychotic drugs counteract autophagy and mitophagy in multiple sclerosis. Proc Natl Acad Sci U S A. 2021;118(24):e2020078118.
  • Duarte-Silva E, Meiry da Rocha Araújo S, Oliveira WH, et al. Sildenafil alleviates murine experimental autoimmune encephalomyelitis by triggering autophagy in the spinal cord. Front Immunol. 2021;12:671511.
  • Wang X, Li B, Liu L, et al. Nicotinamide adenine dinucleotide treatment alleviates the symptoms of experimental autoimmune encephalomyelitis by activating autophagy and inhibiting the NLRP3 inflammasome. Int Immunopharmacol. 2021;90:107092.
  • Arab HH, Al-Shorbagy MY, Saad MA. Activation of autophagy and suppression of apoptosis by dapagliflozin attenuates experimental inflammatory bowel disease in rats: targeting AMPK/mTOR, HMGB1/RAGE and Nrf2/HO-1 pathways. Chem Biol Interact. 2021;335:109368.
  • Guo W, Sun Y, Liu W, et al. Small molecule-driven mitophagy-mediated NLRP3 inflammasome inhibition is responsible for the prevention of colitis-associated cancer. Autophagy. 2014;10(6):972–985.
  • Shao BZ, Wei W, Ke P, et al. Activating cannabinoid receptor 2 alleviates pathogenesis of experimental autoimmune encephalomyelitis via activation of autophagy and inhibiting NLRP3 inflammasome. CNS Neurosci Ther. 2014;20(12):1021–1028.
  • Butera A, Quaranta MT, Crippa L, et al. CD147 targeting by AC-73 induces autophagy and reduces intestinal fibrosis associated with TNBS chronic colitis. J Crohns Colitis. 2022;16(11):1751–1761.
  • Chen C, Zhang Y, Tao M, et al. Atrial natriuretic peptide attenuates colitis via inhibition of the cGAS-STING pathway in colonic epithelial cells. Int J Biol Sci. 2022;18(4):1737–1754.
  • Feng L, Song P, Xu F, et al. cis-Khellactone inhibited the proinflammatory macrophages via promoting autophagy to ameliorate imiquimod-induced psoriasis. J Invest Dermatol. 2019;139(9):1946–1956.
  • Hailfinger S, Schulze-Osthoff K. Impaired autophagy in psoriasis and atopic dermatitis: a new therapeutic target? J Invest Dermatol. 2021;141(12):2775–2777.
  • Park A, Heo T-H. IL-17A-targeting fenofibrate attenuates inflammation in psoriasis by inducing autophagy. Life Sci. 2023;326:121755.
  • Zhang Q, Luo Y, Zheng Q, et al. Itaconate attenuates autoimmune hepatitis via PI3K/AKT/mTOR pathway-mediated inhibition of dendritic cell maturation and autophagy. Heliyon. 2023;9(7):e17551.
  • Fan X, Men R, Wang H, et al. Methylprednisolone decreases mitochondria-mediated apoptosis and autophagy dysfunction in hepatocytes of experimental autoimmune hepatitis model via the akt/mTOR signaling. Front Pharmacol. 2019;10:1189.
  • Li J, Xia Y, Liu T, et al. Protective effects of astaxanthin on ConA-induced autoimmune hepatitis by the JNK/p-JNK pathway-mediated inhibition of autophagy and apoptosis. PLoS One. 2015;10(3):e0120440.
  • Qian R, Chen H, Lin H, et al. The protective roles of allicin on type 1 diabetes mellitus through AMPK/mTOR mediated autophagy pathway. Front Pharmacol. 2023;14:1108730.
  • Wang Y, He D, Ni C, et al. Vitamin D induces autophagy of pancreatic β-cells and enhances insulin secretion. Mol Med Rep. 2016;14(3):2644–2650.
  • Lv F, He Y, Xu H, et al. CD36 aggravates podocyte injury by activating NLRP3 inflammasome and inhibiting autophagy in lupus nephritis. Cell Death Dis. 2022;13(8):729.
  • Zhou W, Wang J, Wang X, et al. Degradation of HDAC10 by autophagy promotes IRF3-mediated antiviral innate immune responses. Sci Signal. 2022;15(765):eabo4356.
  • Gkirtzimanaki K, Kabrani E, Nikoleri D, et al. IFNα impairs autophagic degradation of mtDNA promoting autoreactivity of SLE monocytes in a STING-Dependent fashion. Cell Rep. 2018;25(4):921–933.
  • Takagawa T, Kitani A, Fuss I, et al. An increase in LRRK2 suppresses autophagy and enhances dectin-1-induced immunity in a mouse model of colitis. Sci Transl Med. 2018;10(444):eaan8162.
  • Zhang H, Cui Z, Cheng D, et al. RNF186 regulates EFNB1 (ephrin B1)-EPHB2-induced autophagy in the colonic epithelial cells for the maintenance of intestinal homeostasis. Autophagy. 2021;17(10):3030–3047.
  • Zhao J, Sun Y, Yang H, et al. PLGA-microspheres-carried circGMCL1 protects against Crohn’s colitis through alleviating NLRP3 inflammasome-induced pyroptosis by promoting autophagy. Cell Death Dis. 2022;13(9):782.