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J. Mol. Sci.","IJMS"],"abstract":"<jats:p>The human immune system executes immune defense against foreign antigens, immune surveillance against mutant cells, and immune homeostasis to maintain bodily physiological equilibrium. Transfer RNA (tRNA) is an important part of gene expression regulation. Recent studies have found that aberrant tRNA modifications can disturb the function of the immune system by altering translation efficiency, including regulating immune recognition and signal transduction, as well as influencing apoptosis and autophagy. tRNA modifications are also closely related to the development and occurrence of immune-related disorders such as infections, tumors, and autoimmune diseases. By integrating current research on immune-related tRNA modifications, this review systematically summarizes the mechanisms of tRNA modifications involved in three major immune functions and their relationship with related diseases, encompassing the direct regulation of immune cells and the indirect immune effects mediated through tissue or tumor cells. In addition, some tRNA modifications can also modulate immune responses by affecting tRNA cleavage and the consequent generation of tRNA-derived small RNAs (tsRNAs). Accordingly, this review outlines promising intervention targets and unresolved research bottlenecks, facilitating follow-up investigations into tRNA modification-dependent immune regulation and translational therapeutic research.<\/jats:p>","DOI":"10.3390\/ijms27156937","type":"journal-article","created":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T12:57:56Z","timestamp":1785761876000},"page":"6937","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Transfer RNA Modifications in the Immune System Participate in Disease Pathogenesis"],"prefix":"10.3390","volume":"27","author":[{"given":"Xinke","family":"Ma","sequence":"first","affiliation":[{"name":"Zhejiang Key Laboratory of Medical Epigenetics, Department of Immunology and Pathogenic Biology, School of Basic Medical Sciences, Hangzhou Normal University, Hangzhou 311121, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hejia","family":"Gu","sequence":"additional","affiliation":[{"name":"Zhejiang Key Laboratory of Medical Epigenetics, Department of Immunology and Pathogenic Biology, School of Basic Medical Sciences, Hangzhou Normal University, Hangzhou 311121, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Zhang","sequence":"additional","affiliation":[{"name":"Zhejiang Key Laboratory of Medical Epigenetics, Department of Immunology and Pathogenic Biology, School of Basic Medical Sciences, Hangzhou Normal University, Hangzhou 311121, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanru","family":"Jia","sequence":"additional","affiliation":[{"name":"Zhejiang Key Laboratory of Medical Epigenetics, Department of Immunology and Pathogenic Biology, School of Basic Medical Sciences, Hangzhou Normal University, Hangzhou 311121, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peiying","family":"Li","sequence":"additional","affiliation":[{"name":"Zhejiang Key Laboratory of Medical Epigenetics, Department of Immunology and Pathogenic Biology, School of Basic Medical Sciences, Hangzhou Normal University, Hangzhou 311121, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingjia","family":"Wang","sequence":"additional","affiliation":[{"name":"Zhejiang Key Laboratory of Medical Epigenetics, Department of Immunology and Pathogenic Biology, School of Basic Medical Sciences, Hangzhou Normal University, Hangzhou 311121, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiahui","family":"Wu","sequence":"additional","affiliation":[{"name":"Zhejiang Key Laboratory of Medical Epigenetics, Department of Immunology and Pathogenic Biology, School of Basic Medical Sciences, Hangzhou Normal University, Hangzhou 311121, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8531-4815","authenticated-orcid":false,"given":"Aiwei","family":"Wu","sequence":"additional","affiliation":[{"name":"Zhejiang Key Laboratory of Medical Epigenetics, Department of Immunology and Pathogenic Biology, School of Basic Medical Sciences, Hangzhou Normal University, Hangzhou 311121, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4677-1340","authenticated-orcid":false,"given":"Jing","family":"Wu","sequence":"additional","affiliation":[{"name":"Zhejiang Key Laboratory of Medical Epigenetics, Department of Immunology and Pathogenic Biology, School of Basic Medical Sciences, Hangzhou Normal University, Hangzhou 311121, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1038\/s41573-023-00829-9","article-title":"tRNA therapeutics for genetic diseases","volume":"23","author":"Coller","year":"2024","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1035","DOI":"10.1016\/j.tcb.2023.04.002","article-title":"tRNA modifications: Insights into their role in human cancers","volume":"33","author":"Wang","year":"2023","journal-title":"Trends Cell Biol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"e13391","DOI":"10.1111\/apha.13391","article-title":"The tRNA-associated dysregulation in immune responses and immune diseases","volume":"228","author":"Zhu","year":"2020","journal-title":"Acta Physiol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"12515","DOI":"10.1093\/nar\/gkac1035","article-title":"Structure of Escherichia coli heat shock protein Hsp15 in complex with the ribosomal 50S subunit bearing peptidyl-tRNA","volume":"50","author":"Safdari","year":"2022","journal-title":"Nucleic Acids Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"668","DOI":"10.1016\/j.molcel.2010.01.023","article-title":"tRNA binds to cytochrome c and inhibits caspase activation","volume":"37","author":"Mei","year":"2010","journal-title":"Mol. Cell"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.mib.2020.06.005","article-title":"Probing the diversity and regulation of tRNA modifications","volume":"57","author":"Kimura","year":"2020","journal-title":"Curr. Opin. Microbiol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1038\/s41580-023-00690-z","article-title":"Roles and regulation of tRNA-derived small RNAs in animals","volume":"25","author":"Muthukumar","year":"2024","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Sagi, D., Rak, R., Gingold, H., Adir, I., Maayan, G., Dahan, O., Broday, L., Pilpel, Y., and Rechavi, O. (2016). Tissue- and Time-Specific Expression of Otherwise Identical tRNA Genes. PLoS Genet, 12.","DOI":"10.1371\/journal.pgen.1006264"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1038\/s41392-022-01175-9","article-title":"RNA modifications: Importance in immune cell biology and related diseases","volume":"7","author":"Cui","year":"2022","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"S3","DOI":"10.1016\/j.jaci.2009.12.980","article-title":"Overview of the immune response","volume":"125","author":"Chaplin","year":"2010","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1473","DOI":"10.1007\/s10875-022-01289-3","article-title":"Human Inborn Errors of Immunity: 2022 Update on the Classification from the International Union of Immunological Societies Expert Committee","volume":"42","author":"Tangye","year":"2022","journal-title":"J. Clin. Immunol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1038\/nri2653","article-title":"Intestinal mucosal barrier function in health and disease","volume":"9","author":"Turner","year":"2009","journal-title":"Nat. Rev. Immunol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2897","DOI":"10.3390\/nu7042897","article-title":"The queuine micronutrient: Charting a course from microbe to man","volume":"7","author":"Fergus","year":"2015","journal-title":"Nutrients"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"958","DOI":"10.1261\/rna.1997610","article-title":"Characterization of the human tRNA-guanine transglycosylase: Confirmation of the heterodimeric subunit structure","volume":"16","author":"Chen","year":"2010","journal-title":"RNA"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1080\/15476286.2021.1950980","article-title":"Structural and functional insights into human tRNA guanine transgylcosylase","volume":"18","author":"Sievers","year":"2021","journal-title":"RNA Biol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1371","DOI":"10.1016\/j.jcmgh.2023.02.006","article-title":"Disruption to tRNA Modification by Queuine Contributes to Inflammatory Bowel Disease","volume":"15","author":"Zhang","year":"2023","journal-title":"Cell. Mol. Gastroenterol. Hepatol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1913","DOI":"10.1242\/jcs.060665","article-title":"Claudin-2, a component of the tight junction, forms a paracellular water channel","volume":"123","author":"Rosenthal","year":"2010","journal-title":"J. Cell Sci."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1136\/gut.2006.094375","article-title":"Changes in expression and distribution of claudin 2, 5 and 8 lead to discontinuous tight junctions and barrier dysfunction in active Crohn\u2019s disease","volume":"56","author":"Zeissig","year":"2007","journal-title":"Gut"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"7551","DOI":"10.1128\/MCB.01034-07","article-title":"Wnt\/beta-catenin is essential for intestinal homeostasis and maintenance of intestinal stem cells","volume":"27","author":"Fevr","year":"2007","journal-title":"Mol. Cell. Biol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"6809","DOI":"10.1038\/s41598-026-37299-z","article-title":"TRMT6 mitigates susceptibility and progression of DSS-induced colitis multifacetedly via translational regulation","volume":"16","author":"Zhang","year":"2026","journal-title":"Sci. Rep."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1016\/j.cell.2006.02.015","article-title":"Pathogen recognition and innate immunity","volume":"124","author":"Akira","year":"2006","journal-title":"Cell"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/j.immuni.2005.06.008","article-title":"Suppression of RNA recognition by Toll-like receptors: The impact of nucleoside modification and the evolutionary origin of RNA","volume":"23","author":"Kariko","year":"2005","journal-title":"Immunity"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1084\/jem.20111075","article-title":"The 2\u2032-O-methylation status of a single guanosine controls transfer RNA-mediated Toll-like receptor 7 activation or inhibition","volume":"209","author":"Jockel","year":"2012","journal-title":"J. Exp. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1159\/000375460","article-title":"2\u2032-O-Methylation within Bacterial RNA Acts as Suppressor of TLR7\/TLR8 Activation in Human Innate Immune Cells","volume":"7","author":"Rimbach","year":"2015","journal-title":"J. Innate Immun."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1351","DOI":"10.1261\/rna.044024.113","article-title":"A modified dinucleotide motif specifies tRNA recognition by TLR7","volume":"20","author":"Kaiser","year":"2014","journal-title":"RNA"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"12833","DOI":"10.1093\/nar\/gkaa1123","article-title":"Bacterial tRNA 2\u2032-O-methylation is dynamically regulated under stress conditions and modulates innate immune response","volume":"48","author":"Galvanin","year":"2020","journal-title":"Nucleic Acids Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1663","DOI":"10.1038\/sj.mt.6300240","article-title":"2\u2032-O-methyl-modified RNAs act as TLR7 antagonists","volume":"15","author":"Robbins","year":"2007","journal-title":"Mol. Ther."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"3265","DOI":"10.1172\/JCI26032","article-title":"Endocytosis of HIV-1 activates plasmacytoid dendritic cells via Toll-like receptor-viral RNA interactions","volume":"115","author":"Beignon","year":"2005","journal-title":"J. Clin. Investig."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1016\/S1074-7613(00)80541-5","article-title":"Humoral immunity due to long-lived plasma cells","volume":"8","author":"Slifka","year":"1998","journal-title":"Immunity"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1126\/science.adi1763","article-title":"Antibody production relies on the tRNA inosine wobble modification to meet biased codon demand","volume":"383","author":"Giguere","year":"2024","journal-title":"Science"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1146","DOI":"10.1126\/science.286.5442.1146","article-title":"An adenosine deaminase that generates inosine at the wobble position of tRNAs","volume":"286","author":"Gerber","year":"1999","journal-title":"Science"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"4279","DOI":"10.1016\/j.febslet.2014.09.025","article-title":"A-to-I editing on tRNAs: Biochemical, biological and evolutionary implications","volume":"588","author":"Torres","year":"2014","journal-title":"FEBS Lett."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Lyu, X., Yang, Q., Li, L., Dang, Y., Zhou, Z., Chen, S., and Liu, Y. (2020). Adaptation of codon usage to tRNA I34 modification controls translation kinetics and proteome landscape. PLoS Genet., 16.","DOI":"10.1371\/journal.pgen.1008836"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1038\/s41586-022-04527-1","article-title":"Germinal centre-driven maturation of B cell response to mRNA vaccination","volume":"604","author":"Kim","year":"2022","journal-title":"Nature"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1259","DOI":"10.1084\/jem.20161533","article-title":"Differentiation of germinal center B cells into plasma cells is initiated by high-affinity antigen and completed by Tfh cells","volume":"214","author":"Krautler","year":"2017","journal-title":"J. Exp. Med."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1186\/s13059-015-0779-x","article-title":"Mutation in WDR4 impairs tRNA m(7)G46 methylation and causes a distinct form of microcephalic primordial dwarfism","volume":"16","author":"Shaheen","year":"2015","journal-title":"Genome Biol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1105","DOI":"10.1016\/j.molcel.2019.06.004","article-title":"Put the Pedal to the METTL1: Adding Internal m(7)G Increases mRNA Translation Efficiency and Augments miRNA Processing","volume":"74","author":"Boulias","year":"2019","journal-title":"Mol. Cell"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1016\/j.molcel.2018.06.001","article-title":"Mettl1\/Wdr4-Mediated m(7)G tRNA Methylome Is Required for Normal mRNA Translation and Embryonic Stem Cell Self-Renewal and Differentiation","volume":"71","author":"Lin","year":"2018","journal-title":"Mol. Cell"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1002\/cac2.12273","article-title":"Aberrant translation regulated by METTL1\/WDR4-mediated tRNA N7-methylguanosine modification drives head and neck squamous cell carcinoma progression","volume":"42","author":"Chen","year":"2022","journal-title":"Cancer Commun."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1122","DOI":"10.1002\/hep.32585","article-title":"Eliminating METTL1-mediated accumulation of PMN-MDSCs prevents hepatocellular carcinoma recurrence after radiofrequency ablation","volume":"77","author":"Zeng","year":"2023","journal-title":"Hepatology"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1646","DOI":"10.1038\/s41591-021-01388-5","article-title":"Inherited PD-1 deficiency underlies tuberculosis and autoimmunity in a child","volume":"27","author":"Ogishi","year":"2021","journal-title":"Nat. Med."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"100907","DOI":"10.1016\/j.drup.2022.100907","article-title":"Research progress of therapeutic effects and drug resistance of immunotherapy based on PD-1\/PD-L1 blockade","volume":"66","author":"Pang","year":"2023","journal-title":"Drug Resist. Updat."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Peeters, D., Pico-Knijnenburg, I., Wieringa, D., Rad, M., Cuperus, R., Ruige, M., Froeling, F., Zijp, G.W., van der Burg, M., and Driessen, G.J.A. (2022). AKT Hyperphosphorylation and T Cell Exhaustion in Down Syndrome. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.724436"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1555","DOI":"10.1136\/gutjnl-2022-327230","article-title":"Targeting tumour-intrinsic N(7)-methylguanosine tRNA modification inhibits MDSC recruitment and improves anti-PD-1 efficacy","volume":"72","author":"Liu","year":"2023","journal-title":"Gut"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1186\/s12943-023-01809-8","article-title":"METTL1 promotes tumorigenesis through tRNA-derived fragment biogenesis in prostate cancer","volume":"22","author":"Dietmann","year":"2023","journal-title":"Mol. Cancer"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1293","DOI":"10.1016\/j.cell.2018.05.060","article-title":"Single-Cell Map of Diverse Immune Phenotypes in the Breast Tumor Microenvironment","volume":"174","author":"Azizi","year":"2018","journal-title":"Cell"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"2156","DOI":"10.1016\/j.celrep.2019.07.068","article-title":"Re-education of Tumor-Associated Macrophages by CXCR2 Blockade Drives Senescence and Tumor Inhibition in Advanced Prostate Cancer","volume":"28","author":"Mirenda","year":"2019","journal-title":"Cell. Rep."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1530\/ERC-18-0284","article-title":"Inhibition of TAMs improves the response to docetaxel in castration-resistant prostate cancer","volume":"26","author":"Guan","year":"2019","journal-title":"Endocr. Relat. Cancer"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1038\/nrclinonc.2016.217","article-title":"Tumour-associated macrophages as treatment targets in oncology","volume":"14","author":"Mantovani","year":"2017","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Luo, H., Chen, D., Zhou, J., Wang, D., Du, Q., Cai, Q., Lv, S., Zhao, X., Zhang, G., and Tan, Y. (2025). Cepharanthine Enhances MHC-I Antigen Presentation and Anti-Tumor Immunity in Melanoma via Autophagy Inhibition. Cells, 14.","DOI":"10.3390\/cells14161231"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1038\/ncb2152","article-title":"AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1","volume":"13","author":"Kim","year":"2011","journal-title":"Nat. Cell Biol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1478","DOI":"10.1038\/s41467-022-29125-7","article-title":"N(7)-methylguanosine tRNA modification promotes esophageal squamous cell carcinoma tumorigenesis via the RPTOR\/ULK1\/autophagy axis","volume":"13","author":"Han","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1083\/jcb.200811106","article-title":"Angiogenin cleaves tRNA and promotes stress-induced translational repression","volume":"185","author":"Yamasaki","year":"2009","journal-title":"J. Cell Biol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1590","DOI":"10.1101\/gad.586710","article-title":"RNA methylation by Dnmt2 protects transfer RNAs against stress-induced cleavage","volume":"24","author":"Schaefer","year":"2010","journal-title":"Genes Dev."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"2533","DOI":"10.1093\/nar\/gky1250","article-title":"Transfer RNA demethylase ALKBH3 promotes cancer progression via induction of tRNA-derived small RNAs","volume":"47","author":"Chen","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"ref_56","first-page":"418","article-title":"Granzyme B\u2013Activated p53 interacts with Bcl-2 to promote cytotoxic lymphocyte-mediated apoptosis","volume":"194","author":"Ziani","year":"2015","journal-title":"J. Immunol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1326","DOI":"10.1016\/j.cmet.2025.03.014","article-title":"Cytosolic cytochrome c represses ferroptosis","volume":"37","author":"Song","year":"2025","journal-title":"Cell Metab."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1038\/s41584-024-01093-w","article-title":"TYK2: An emerging therapeutic target in rheumatic disease","volume":"20","author":"Morand","year":"2024","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Rossano, M., Conti, E.A., Bocca, P., Volpi, S., Mastrangelo, A., Cavalli, R., Gattorno, M., Minoia, F., and Filocamo, G. (2023). Novel heterozygous TREX1 mutation in a juvenile systemic lupus erythematosus patient with severe cutaneous involvement treated successfully with Jak-inhibitors: A case report. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1288675"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"932","DOI":"10.1038\/s43018-021-00238-0","article-title":"Targeting PUS7 suppresses tRNA pseudouridylation and glioblastoma tumorigenesis","volume":"2","author":"Cui","year":"2021","journal-title":"Nat. Cancer"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"11083","DOI":"10.1074\/jbc.M115.711895","article-title":"Rhein Inhibits AlkB Repair Enzymes and Sensitizes Cells to Methylated DNA Damage","volume":"291","author":"Li","year":"2016","journal-title":"J. Biol. Chem."},{"key":"ref_62","first-page":"39","article-title":"Improving the bioavailability and anticancer effect of the PCA-1\/ALKBH3 inhibitor HUHS015 using sodium salt","volume":"29","author":"Mabuchi","year":"2015","journal-title":"Vivo"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1111\/joim.12395","article-title":"Human autoimmune diseases: A comprehensive update","volume":"278","author":"Wang","year":"2015","journal-title":"J. Intern. Med."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"102438","DOI":"10.1016\/j.jaut.2020.102438","article-title":"Clinical significance of miRNAs in autoimmunity","volume":"109","author":"Zhang","year":"2020","journal-title":"J. Autoimmun."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1038\/nri2550","article-title":"Autoimmune T cell responses in the central nervous system","volume":"9","author":"Goverman","year":"2009","journal-title":"Nat. Rev. Immunol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"2078","DOI":"10.1001\/jama.2022.14236","article-title":"What Is Multiple Sclerosis?","volume":"328","author":"Marcus","year":"2022","journal-title":"JAMA"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1038\/nrc2292","article-title":"Thiopurines in current medical practice: Molecular mechanisms and contributions to therapy-related cancer","volume":"8","author":"Karran","year":"2008","journal-title":"Nat. Rev. Cancer"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/0167-4781(84)90124-6","article-title":"Substrate and inhibitor specificity of tRNA-guanine ribosyltransferase","volume":"781","author":"Farkas","year":"1984","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_69","first-page":"2029","article-title":"In vivo modification of tRNA with an artificial nucleobase leads to full disease remission in an animal model of multiple sclerosis","volume":"45","author":"Varghese","year":"2017","journal-title":"Nucleic Acids Res."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1102","DOI":"10.1016\/S0022-3565(24)36860-0","article-title":"Tissue specific toxicities of the anticancer drug 6-thioguanine is dependent on the Hprt status in transgenic mice","volume":"282","author":"Aubrecht","year":"1997","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Malyshkina, A., Bruggemann, A., Paschen, A., and Dittmer, U. (2023). Cytotoxic CD4(+) T cells in chronic viral infections and cancer. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1271236"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"eadp2919","DOI":"10.1126\/sciadv.adp2919","article-title":"Pseudokinase STK40 promotes TH1 and TH17 cell differentiation by targeting FOXO transcription factors","volume":"10","author":"Tao","year":"2024","journal-title":"Sci. Adv."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1016\/j.jaut.2013.01.004","article-title":"E4BP4 overexpression: A protective mechanism in CD4+ T cells from SLE patients","volume":"41","author":"Zhao","year":"2013","journal-title":"J. Autoimmun."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"4046","DOI":"10.1038\/s41467-022-31519-6","article-title":"Single cell sequencing identifies clonally expanded synovial CD4(+) T(PH) cells expressing GPR56 in rheumatoid arthritis","volume":"13","author":"Argyriou","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1038\/nm0297-183","article-title":"Murine psoriasis-like disorder induced by naive CD4+ T cells","volume":"3","author":"Schon","year":"1997","journal-title":"Nat. Med."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"e2204269120","DOI":"10.1073\/pnas.2204269120","article-title":"Identification of a unique subset of tissue-resident memory CD4(+) T cells in Crohn\u2019s disease","volume":"120","author":"Yokoi","year":"2023","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1038\/nature16998","article-title":"The dynamic N(1)-methyladenosine methylome in eukaryotic messenger RNA","volume":"530","author":"Dominissini","year":"2016","journal-title":"Nature"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1038\/nchembio.2040","article-title":"Transcriptome-wide mapping reveals reversible and dynamic N(1)-methyladenosine methylome","volume":"12","author":"Li","year":"2016","journal-title":"Nat. Chem. Biol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1016\/j.immuni.2011.09.021","article-title":"The transcription factor Myc controls metabolic reprogramming upon T lymphocyte activation","volume":"35","author":"Wang","year":"2011","journal-title":"Immunity"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"e53725","DOI":"10.7554\/eLife.53725","article-title":"Quantitative analysis of how Myc controls T cell proteomes and metabolic pathways during T cell activation","volume":"9","author":"Marchingo","year":"2020","journal-title":"Elife"},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Hydbring, P., Castell, A., and Larsson, L.G. (2017). MYC Modulation around the CDK2\/p27\/SKP2 Axis. Genes, 8.","DOI":"10.3390\/genes8070174"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1433","DOI":"10.1038\/s41590-022-01301-3","article-title":"tRNA-m(1)A modification promotes T cell expansion via efficient MYC protein synthesis","volume":"23","author":"Liu","year":"2022","journal-title":"Nat. Immunol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1016\/j.bbrc.2020.04.114","article-title":"The potential role of tRNAs and small RNAs derived from tRNAs in the occurrence and development of systemic lupus erythematosus","volume":"527","author":"Xu","year":"2020","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"9368","DOI":"10.1093\/nar\/gkac698","article-title":"Human TRUB1 is a highly conserved pseudouridine synthase responsible for the formation of Psi55 in mitochondrial tRNAAsn, tRNAGln, tRNAGlu and tRNAPro","volume":"50","author":"Jia","year":"2022","journal-title":"Nucleic Acids Res."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"752","DOI":"10.1016\/j.immuni.2024.03.002","article-title":"DAMPs and DAMP-sensing receptors in inflammation and diseases","volume":"57","author":"Ma","year":"2024","journal-title":"Immunity"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1038\/s41577-022-00760-x","article-title":"Mitochondrial control of inflammation","volume":"23","author":"Marchi","year":"2023","journal-title":"Nat. Rev. Immunol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1038\/ncprheum0531","article-title":"Mechanisms of disease: A \u2018DAMP\u2019 view of inflammatory arthritis","volume":"3","author":"Foell","year":"2007","journal-title":"Nat. Clin. Pract. Rheumatol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"e27","DOI":"10.4110\/in.2018.18.e27","article-title":"Damage-Associated Molecular Patterns in Inflammatory Diseases","volume":"18","author":"Roh","year":"2018","journal-title":"Immune Netw."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"e109353","DOI":"10.15252\/embj.2021109353","article-title":"Elp3-mediated codon-dependent translation promotes mTORC2 activation and regulates macrophage polarization","volume":"41","author":"Chen","year":"2022","journal-title":"EMBO J."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1016\/S0092-8674(00)80595-4","article-title":"Akt promotes cell survival by phosphorylating and inhibiting a Forkhead transcription factor","volume":"96","author":"Brunet","year":"1999","journal-title":"Cell"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"817","DOI":"10.1016\/j.immuni.2016.09.016","article-title":"Metabolic Reprogramming Mediated by the mTORC2-IRF4 Signaling Axis Is Essential for Macrophage Alternative Activation","volume":"45","author":"Huang","year":"2016","journal-title":"Immunity"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"e3065","DOI":"10.1002\/jmr.3065","article-title":"A brief account of evolution of assays to study carbohydrate-protein interaction","volume":"37","author":"Ballal","year":"2024","journal-title":"J. Mol. Recognit."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1186\/s13550-024-01129-y","article-title":"[(68)Ga]Ga-FAPI versus 2-[(18)F]FDG PET\/CT in patients with autoimmune thyroiditis: A case control study","volume":"14","author":"Pabst","year":"2024","journal-title":"EJNMMI Res."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"7096","DOI":"10.1111\/febs.15736","article-title":"Human transfer RNA modopathies: Diseases caused by aberrations in transfer RNA modifications","volume":"288","author":"Chujo","year":"2021","journal-title":"FEBS J."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/15\/6937\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T13:09:05Z","timestamp":1785762545000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/15\/6937"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,2]]},"references-count":94,"journal-issue":{"issue":"15","published-online":{"date-parts":[[2026,8]]}},"alternative-id":["ijms27156937"],"URL":"https:\/\/doi.org\/10.3390\/ijms27156937","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,2]]}}}