{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T22:34:52Z","timestamp":1789079692024,"version":"build-2803163510"},"reference-count":133,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2025,5,16]],"date-time":"2025-05-16T00:00:00Z","timestamp":1747353600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Inflammatory bowel disease (IBD), which includes Crohn\u2019s Disease (CD) and ulcerative colitis (UC), is characterized by chronic inflammation of the gastrointestinal tract. A key component of the inflammatory pathway in IBD is interleukin 23 (IL-23), which promotes the differentiation and maintenance of Th17 cells. These cells are major contributors to intestinal inflammation and the release of pro-inflammatory cytokines. A dysregulated IL-23\/Th17 axis can lead to excessive gut inflammation. Notably, IL-23 affects Th17 cell responses differently in UC and CD, fostering IL-17 production in UC and interferon-gamma (IFN-\u03b3) production in CD. Genetic studies have pinpointed specific variants of the IL-23 receptor (IL23R) gene that confer protection against IBD. The R381Q (rs11209026) variant has been linked to a reduced risk of developing both CD and UC. Additionally, other variants, such as G149R (rs76418789) and V362I (rs41313262), inhibit IL23R function by disrupting intracellular trafficking and protein stability. This disruption results in decreased phosphorylation of downstream signal transducers, such as STAT3 and STAT4, and reduced IL23R expression on the cell surface, ultimately dampening the activation of pro-inflammatory pathways. The protective effects of these genetic variants underscore the IL-23\/IL23R pathway as a significant therapeutic target in IBD management. Therapies designed to modulate this pathway have the potential to reduce pro-inflammatory cytokine production and enhance anti-inflammatory mechanisms. Ongoing research into the IL23R gene and its variants continues to provide valuable insights, paving the way for more targeted and effective treatments for IBD patients.<\/jats:p>","DOI":"10.3390\/ijms26104775","type":"journal-article","created":{"date-parts":[[2025,5,16]],"date-time":"2025-05-16T06:57:28Z","timestamp":1747378648000},"page":"4775","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Targeting the IL-23 Receptor Gene: A Promising Approach in Inflammatory Bowel Disease Treatment"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-7790-7845","authenticated-orcid":false,"given":"Ploutarchos","family":"Pastras","sequence":"first","affiliation":[{"name":"Division of Gastroenterology, Department of Internal Medicine, University of Patras, 26504 Patras, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4489-1485","authenticated-orcid":false,"given":"Ioanna","family":"Aggeletopoulou","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Department of Internal Medicine, University of Patras, 26504 Patras, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Konstantinos","family":"Papantoniou","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Department of Internal Medicine, University of Patras, 26504 Patras, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3094-8209","authenticated-orcid":false,"given":"Christos","family":"Triantos","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Department of Internal Medicine, University of Patras, 26504 Patras, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1185","DOI":"10.1080\/00365521.2017.1349173","article-title":"Mucosal immune system of the gastrointestinal tract: Maintaining balance between the good and the bad","volume":"52","author":"Ahluwalia","year":"2017","journal-title":"Scand. J. Gastroenterol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.cgh.2019.07.005","article-title":"Ulcerative Colitis and Crohn\u2019s Disease Have Similar Burden and Goals for Treatment","volume":"18","author":"Ananthakrishnan","year":"2020","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"7247238","DOI":"10.1155\/2019\/7247238","article-title":"A Comprehensive Review and Update on the Pathogenesis of Inflammatory Bowel Disease","volume":"2019","author":"Guan","year":"2019","journal-title":"J. Immunol. Res."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1093\/ecco-jcc\/jjw168","article-title":"3rd European Evidence-based Consensus on the Diagnosis and Management of Crohn\u2019s Disease 2016: Part 1: Diagnosis and Medical Management","volume":"11","author":"Dignass","year":"2017","journal-title":"J. Crohns Colitis"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"6","DOI":"10.3748\/wjg.v20.i1.6","article-title":"Immunopathology of inflammatory bowel disease","volume":"20","author":"Wallace","year":"2014","journal-title":"World J. Gastroenterol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1038\/nature06005","article-title":"Unravelling the pathogenesis of inflammatory bowel disease","volume":"448","author":"Xavier","year":"2007","journal-title":"Nature"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"3255","DOI":"10.3748\/wjg.v20.i12.3255","article-title":"Dysregulation of mucosal immune response in pathogenesis of inflammatory bowel disease","volume":"20","author":"Xu","year":"2014","journal-title":"World J. Gastroenterol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1038\/nrgastro.2015.186","article-title":"Immunopathogenesis of IBD: Current state of the art","volume":"13","author":"Fiocchi","year":"2016","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"91","DOI":"10.3748\/wjg.v20.i1.91","article-title":"Inflammatory bowel disease: Pathogenesis","volume":"20","author":"Zhang","year":"2014","journal-title":"World J. Gastroenterol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1252","DOI":"10.1016\/j.cgh.2020.01.028","article-title":"Changing Global Epidemiology of Inflammatory Bowel Diseases: Sustaining Health Care Delivery Into the 21st Century","volume":"18","author":"Ananthakrishnan","year":"2020","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"e00213","DOI":"10.14309\/ctg.0000000000000213","article-title":"Host Genetic and Gut Microbial Signatures in Familial Inflammatory Bowel Disease","volume":"11","author":"Park","year":"2020","journal-title":"Clin. Transl. Gastroenterol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1038\/nature11582","article-title":"Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease","volume":"491","author":"Jostins","year":"2012","journal-title":"Nature"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1461","DOI":"10.1126\/science.1135245","article-title":"A genome-wide association study identifies IL23R as an inflammatory bowel disease gene","volume":"314","author":"Duerr","year":"2006","journal-title":"Science"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1146\/annurev.immunol.22.012703.104758","article-title":"Discovery and Biology of IL-23 and IL-27: Related but Functionally Distinct Regulators of Inflammation","volume":"25","author":"Kastelein","year":"2007","journal-title":"Annu. Rev. Immunol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"289","DOI":"10.2147\/ITT.S282466","article-title":"All are Equal, Some are More Equal: Targeting IL 12 and 23 in IBD\u2014A Clinical Perspective","volume":"9","author":"Jefremow","year":"2020","journal-title":"ImmunoTargets Ther."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Lupardus, P.J., and Garcia, K.C. (2008). The structure of Interleukin-23 reveals the molecular basis of p40 subunit sharing with IL-12. J. Mol. Biol., 382.","DOI":"10.1016\/j.jmb.2008.07.051"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1582","DOI":"10.1182\/blood-2004-05-1718","article-title":"Extracellular nucleotide signaling by P2 receptors inhibits IL-12 and enhances IL-23 expression in human dendritic cells: A novel role for the cAMP pathway","volume":"105","author":"Schnurr","year":"2005","journal-title":"Blood"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1136\/gutjnl-2016-313235","article-title":"A microbial signature for Crohn\u2019s disease","volume":"66","author":"Pascal","year":"2017","journal-title":"Gut"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1172\/JCI200317464","article-title":"Constitutive p40 promoter activation and IL-23 production in the terminal ileum mediated by dendritic cells","volume":"112","author":"Becker","year":"2003","journal-title":"J. Clin. Investig."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1189\/jlb.0810456","article-title":"The increased expression of IL-23 in inflammatory bowel disease promotes intraepithelial and lamina propria lymphocyte inflammatory responses and cytotoxicity","volume":"89","author":"Liu","year":"2011","journal-title":"J. Leukoc. Biol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1097\/00054725-200501000-00003","article-title":"Expression of interleukin-12-related cytokine transcripts in inflammatory bowel disease: Elevated interleukin-23p19 and interleukin-27p28 in Crohn\u2019s disease but not in ulcerative colitis","volume":"11","author":"Schmidt","year":"2005","journal-title":"Inflamm. Bowel Dis."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"814","DOI":"10.1136\/gutjnl-2017-315671","article-title":"Expansion of IL-23 receptor bearing TNFR2+ T cells is associated with molecular resistance to anti-TNF therapy in Crohn\u2019s disease","volume":"68","author":"Schmitt","year":"2019","journal-title":"Gut"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"4560","DOI":"10.1073\/pnas.0400983101","article-title":"Human IL-23-producing type 1 macrophages promote but IL-10-producing type 2 macrophages subvert immunity to (myco)bacteria","volume":"101","author":"Verreck","year":"2004","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"37692","DOI":"10.1074\/jbc.M105927200","article-title":"Toll-like receptor 2 (TLR2) and TLR4 differentially activate human dendritic cells","volume":"276","author":"Re","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"764","DOI":"10.1189\/jlb.1003461","article-title":"Streptococcus pyogenes and Lactobacillus rhamnosus differentially induce maturation and production of Th1-type cytokines and chemokines in human monocyte-derived dendritic cells","volume":"75","author":"Veckman","year":"2004","journal-title":"J. Leukoc. Biol."},{"key":"ref_26","first-page":"2269","article-title":"Unique CD14 intestinal macrophages contribute to the pathogenesis of Crohn disease via IL-23\/IFN-gamma axis","volume":"118","author":"Kamada","year":"2008","journal-title":"J. Clin. Investig."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1016\/j.immuni.2013.08.035","article-title":"The intracellular sensor NOD2 induces microRNA-29 expression in human dendritic cells to limit IL-23 release","volume":"39","author":"Brain","year":"2013","journal-title":"Immunity"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1038\/nri.2016.4","article-title":"Purinergic regulation of the immune system","volume":"16","author":"Cekic","year":"2016","journal-title":"Nat. Rev. Immunol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1201","DOI":"10.1016\/j.cell.2019.03.018","article-title":"Metabolic and Innate Immune Cues Merge into a Specific Inflammatory Response via the UPR","volume":"177","author":"Mogilenko","year":"2019","journal-title":"Cell"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1016\/j.cell.2019.12.017","article-title":"FAMIN Is a Multifunctional Purine Enzyme Enabling the Purine Nucleotide Cycle","volume":"180","author":"Cader","year":"2020","journal-title":"Cell"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1023","DOI":"10.1136\/gutjnl-2020-321731","article-title":"Deconvolution of monocyte responses in inflammatory bowel disease reveals an IL-1 cytokine network that regulates IL-23 in genetic and acquired IL-10 resistance","volume":"70","author":"Aschenbrenner","year":"2021","journal-title":"Gut"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1038\/ni.3306","article-title":"Molecular control of activation and priming in macrophages","volume":"17","author":"Glass","year":"2016","journal-title":"Nat. Immunol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1586\/1744666X.2014.894886","article-title":"The CXCL8\/IL-8 chemokine family and its receptors in inflammatory diseases","volume":"10","author":"Russo","year":"2014","journal-title":"Expert. Rev. Clin. Immunol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1121","DOI":"10.1016\/j.cell.2006.07.035","article-title":"The orphan nuclear receptor RORgammat directs the differentiation program of proinflammatory IL-17+ T helper cells","volume":"126","author":"Ivanov","year":"2006","journal-title":"Cell"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1016\/j.cell.2009.09.033","article-title":"Induction of intestinal Th17 cells by segmented filamentous bacteria","volume":"139","author":"Ivanov","year":"2009","journal-title":"Cell"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"943","DOI":"10.1007\/s00011-014-0768-7","article-title":"Elevated levels of Th17 cells and Th17-related cytokines are associated with disease activity in patients with inflammatory bowel disease","volume":"63","author":"Jiang","year":"2014","journal-title":"Inflamm. Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/j.immuni.2006.01.001","article-title":"TGFbeta in the context of an inflammatory cytokine milieu supports de novo differentiation of IL-17-producing T cells","volume":"24","author":"Veldhoen","year":"2006","journal-title":"Immunity"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1038\/nature06878","article-title":"TGF-beta-induced Foxp3 inhibits T(H)17 cell differentiation by antagonizing RORgammat function","volume":"453","author":"Zhou","year":"2008","journal-title":"Nature"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"967","DOI":"10.1038\/ni1488","article-title":"IL-6 programs T(H)-17 cell differentiation by promoting sequential engagement of the IL-21 and IL-23 pathways","volume":"8","author":"Zhou","year":"2007","journal-title":"Nat. Immunol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1016\/S1074-7613(00)00070-4","article-title":"Novel p19 protein engages IL-12p40 to form a cytokine, IL-23, with biological activities similar as well as distinct from IL-12","volume":"13","author":"Oppmann","year":"2000","journal-title":"Immunity"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"568","DOI":"10.1038\/ni.2031","article-title":"The encephalitogenicity of T(H)17 cells is dependent on IL-1- and IL-23-induced production of the cytokine GM-CSF","volume":"12","author":"Ciric","year":"2011","journal-title":"Nat. Immunol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"2271","DOI":"10.1084\/jem.20061308","article-title":"Interleukin (IL)-22 and IL-17 are coexpressed by Th17 cells and cooperatively enhance expression of antimicrobial peptides","volume":"203","author":"Liang","year":"2006","journal-title":"J. Exp. Med."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1016\/j.immuni.2008.11.005","article-title":"Late developmental plasticity in the T helper 17 lineage","volume":"30","author":"Lee","year":"2009","journal-title":"Immunity"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Schmitt, H., Neurath, M.F., and Atreya, R. (2021). Role of the IL23\/IL17 Pathway in Crohn\u2019s Disease. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.622934"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"ii3","DOI":"10.1093\/ecco-jcc\/jjac034","article-title":"Interleukin-23 in the Pathogenesis of Inflammatory Bowel Disease and Implications for Therapeutic Intervention","volume":"16","author":"Sewell","year":"2022","journal-title":"J. Crohns Colitis."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1599","DOI":"10.1038\/ajg.2016.298","article-title":"A Randomized, Double-Blind, Placebo-Controlled Phase 2 Study of Brodalumab in Patients With Moderate-to-Severe Crohn\u2019s Disease","volume":"111","author":"Targan","year":"2016","journal-title":"Am. J. Gastroenterol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1131","DOI":"10.1136\/gut.2005.079392","article-title":"Fontolizumab, a humanised anti-interferon gamma antibody, demonstrates safety and clinical activity in patients with moderate to severe Crohn\u2019s disease","volume":"55","author":"Hommes","year":"2006","journal-title":"Gut"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"e1207","DOI":"10.1002\/iid3.1207","article-title":"Knockdown of TOP2A suppresses IL-17 signaling pathway and alleviates the progression of ulcerative colitis","volume":"12","author":"Li","year":"2024","journal-title":"Immun. Inflamm. Dis."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1016\/j.immuni.2010.08.010","article-title":"Interleukin-23 drives intestinal inflammation through direct activity on T cells","volume":"33","author":"Ahern","year":"2010","journal-title":"Immunity"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"882","DOI":"10.1053\/j.gastro.2010.05.040","article-title":"Imbalance of NKp44(+)NKp46(-) and NKp44(-)NKp46(+) natural killer cells in the intestinal mucosa of patients with Crohn\u2019s disease","volume":"139","author":"Takayama","year":"2010","journal-title":"Gastroenterology"},{"key":"ref_51","first-page":"342.e5","article-title":"LAG3+ Regulatory T Cells Restrain Interleukin-23-Producing CX3CR1+ Gut-Resident Macrophages during Group 3 Innate Lymphoid Cell-Driven Colitis","volume":"49","author":"Jain","year":"2018","journal-title":"Immunity"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1146\/annurev.immunol.021908.132657","article-title":"Regulatory lymphocytes and intestinal inflammation","volume":"27","author":"Izcue","year":"2009","journal-title":"Annu. Rev. Immunol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1461","DOI":"10.1093\/intimm\/5.11.1461","article-title":"Phenotypically distinct subsets of CD4+ T cells induce or protect from chronic intestinal inflammation in C. B-17 scid mice","volume":"5","author":"Powrie","year":"1993","journal-title":"Int. Immunol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"3939","DOI":"10.4049\/jimmunol.170.8.3939","article-title":"Cutting edge: Cure of colitis by CD4+CD25+ regulatory T cells","volume":"170","author":"Mottet","year":"2003","journal-title":"J. Immunol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1016\/j.immuni.2008.02.019","article-title":"Interleukin-23 restrains regulatory T cell activity to drive T cell-dependent colitis","volume":"28","author":"Izcue","year":"2008","journal-title":"Immunity"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"112128","DOI":"10.1016\/j.celrep.2023.112128","article-title":"Interleukin-23 receptor signaling impairs the stability and function of colonic regulatory T cells","volume":"42","author":"Jacobse","year":"2023","journal-title":"Cell Rep."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1571","DOI":"10.1084\/jem.20140678","article-title":"CX3CR1+ mononuclear phagocytes support colitis-associated innate lymphoid cell production of IL-22","volume":"211","author":"Longman","year":"2014","journal-title":"J. Exp. Med."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"eaav1080","DOI":"10.1126\/sciimmunol.aav1080","article-title":"IL-23 and IL-2 activation of STAT5 is required for optimal IL-22 production in ILC3s during colitis","volume":"5","author":"Fong","year":"2020","journal-title":"Sci. Immunol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.immuni.2013.10.021","article-title":"Induction of innate lymphoid cell-derived interleukin-22 by the transcription factor STAT3 mediates protection against intestinal infection","volume":"40","author":"Guo","year":"2014","journal-title":"Immunity"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1127","DOI":"10.1084\/jem.20101712","article-title":"IL-23-responsive innate lymphoid cells are increased in inflammatory bowel disease","volume":"208","author":"Geremia","year":"2011","journal-title":"J. Exp. Med."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1038\/mi.2013.33","article-title":"IL-23R+ innate lymphoid cells induce colitis via interleukin-22-dependent mechanism","volume":"7","author":"Eken","year":"2014","journal-title":"Mucosal Immunol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"e20192195","DOI":"10.1084\/jem.20192195","article-title":"The role of IL-22 in intestinal health and disease","volume":"217","author":"Keir","year":"2020","journal-title":"J. Exp. Med."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"947","DOI":"10.1016\/j.immuni.2008.11.003","article-title":"Innate and adaptive interleukin-22 protects mice from inflammatory bowel disease","volume":"29","author":"Zenewicz","year":"2008","journal-title":"Immunity"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1038\/nm1720","article-title":"Interleukin-22 mediates early host defense against attaching and effacing bacterial pathogens","volume":"14","author":"Zheng","year":"2008","journal-title":"Nat. Med."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"578","DOI":"10.1136\/gutjnl-2019-318483","article-title":"Interleukin-22 orchestrates a pathological endoplasmic reticulum stress response transcriptional programme in colonic epithelial cells","volume":"69","author":"Powell","year":"2020","journal-title":"Gut"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"2868","DOI":"10.1084\/jem.20171029","article-title":"ATG16L1 orchestrates interleukin-22 signaling in the intestinal epithelium via cGAS-STING","volume":"215","author":"Aden","year":"2018","journal-title":"J. Exp. Med."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1038\/mi.2012.24","article-title":"The role of neutrophils during intestinal inflammation","volume":"5","author":"Fournier","year":"2012","journal-title":"Mucosal Immunol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1116","DOI":"10.1016\/j.immuni.2012.08.025","article-title":"Dysregulated hematopoietic stem and progenitor cell activity promotes interleukin-23-driven chronic intestinal inflammation","volume":"37","author":"Griseri","year":"2012","journal-title":"Immunity"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1016\/j.immuni.2015.07.008","article-title":"Granulocyte Macrophage Colony-Stimulating Factor-Activated Eosinophils Promote Interleukin-23 Driven Chronic Colitis","volume":"43","author":"Griseri","year":"2015","journal-title":"Immunity"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1136\/gutjnl-2018-316830","article-title":"IL23 induces IL23R recycling and amplifies innate receptor-induced signalling and cytokines in human macrophages, and the IBD-protective IL23R R381Q variant modulates these outcomes","volume":"69","author":"Sun","year":"2020","journal-title":"Gut"},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Chognard, G., Bellemare, L., Pelletier, A.N., Dominguez-Punaro, M.C., Beauchamp, C., Guyon, M.J., Charron, G., Morin, N., Sivanesan, D., and Kuchroo, V. (2014). The dichotomous pattern of IL-12r and IL-23R expression elucidates the role of IL-12 and IL-23 in inflammation. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0089092"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"5699","DOI":"10.4049\/jimmunol.168.11.5699","article-title":"A receptor for the heterodimeric cytokine IL-23 is composed of IL-12Rbeta1 and a novel cytokine receptor subunit, IL-23R","volume":"168","author":"Parham","year":"2002","journal-title":"J. Immunol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/j.tig.2009.01.001","article-title":"GWA studies: Rewriting the story of IBD","volume":"25","author":"Budarf","year":"2009","journal-title":"Trends Genet."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1038\/mi.2008.26","article-title":"IL-22 in mucosal immunity","volume":"1","author":"Ouyang","year":"2008","journal-title":"Mucosal Immunol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1038\/ni.1698","article-title":"The interleukin 23 receptor is essential for the terminal differentiation of interleukin 17-producing effector T helper cells in vivo","volume":"10","author":"McGeachy","year":"2009","journal-title":"Nat. Immunol."},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Guo, W., Luo, C., Wang, C., Zhu, Y., Wang, X., Gao, X., and Yao, W. (2012). Protection against Th17 cells differentiation by an interleukin-23 receptor cytokine-binding homology region. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0045625"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1090","DOI":"10.1002\/ibd.20894","article-title":"Interleukin-23\/Th17 pathways and inflammatory bowel disease","volume":"15","author":"Abraham","year":"2009","journal-title":"Inflamm. Bowel Dis."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1111\/j.1572-0241.2007.01661.x","article-title":"Association between genetic variants in the IL-23R gene and early-onset Crohn\u2019s disease: Results from a case-control and family-based study among Canadian children","volume":"103","author":"Amre","year":"2008","journal-title":"Am. J. Gastroenterol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"596","DOI":"10.1038\/ng2032","article-title":"Genome-wide association study identifies new susceptibility loci for Crohn disease and implicates autophagy in disease pathogenesis","volume":"39","author":"Rioux","year":"2007","journal-title":"Nat. Genet."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"8673","DOI":"10.1074\/jbc.M116.715870","article-title":"IL23R (Interleukin 23 Receptor) Variants Protective against Inflammatory Bowel Diseases (IBD) Display Loss of Function due to Impaired Protein Stability and Intracellular Trafficking","volume":"291","author":"Sivanesan","year":"2016","journal-title":"J. Biol. Chem."},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Krause-Kyora, B., da Silva, N.A., Kaplan, E., Kolbe, D., Archaeological Civilization Disease Consortium, Wohlers, I., Busch, H., Ellinghaus, D., Caliebe, A., and Sezgin, E. (2025). Neolithic introgression of IL23R-related protection against chronic inflammatory bowel diseases in modern Europeans. EBioMedicine, 113.","DOI":"10.1016\/j.ebiom.2025.105591"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1007\/s00011-019-01296-y","article-title":"Genetic association between IL23R rs11209026 and rs10889677 polymorphisms and risk of Crohn\u2019s disease and ulcerative colitis: Evidence from 41 studies","volume":"69","author":"Zhu","year":"2020","journal-title":"Inflamm. Res."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"539461","DOI":"10.1155\/2010\/539461","article-title":"IL23R and IL12B SNPs and Haplotypes Strongly Associate with Crohn\u2019s Disease Risk in a New Zealand Population","volume":"2010","author":"Ferguson","year":"2010","journal-title":"Gastroenterol. Res. Pract."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"4127","DOI":"10.1073\/pnas.0711580105","article-title":"Contribution of positively charged flanking residues to the insertion of transmembrane helices into the endoplasmic reticulum","volume":"105","author":"Lundin","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"977","DOI":"10.1016\/j.cgh.2007.05.002","article-title":"Replication of an association between IL23R gene polymorphism with inflammatory bowel disease","volume":"5","author":"Oliver","year":"2007","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1397","DOI":"10.1111\/j.1365-2222.2012.04022.x","article-title":"Targeting IL-23 by employing a p40 peptide-based vaccine ameliorates murine allergic skin and airway inflammation","volume":"42","author":"Guan","year":"2012","journal-title":"Clin. Exp. Allergy"},{"key":"ref_87","doi-asserted-by":"crossref","unstructured":"Pidasheva, S., Trifari, S., Phillips, A., Hackney, J.A., Ma, Y., Smith, A., Sohn, S.J., Spits, H., Little, R.D., and Behrens, T.W. (2011). Functional studies on the IBD susceptibility gene IL23R implicate reduced receptor function in the protective genetic variant R381Q. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0025038"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"9560","DOI":"10.1073\/pnas.1017854108","article-title":"Inflammatory disease protective R381Q IL23 receptor polymorphism results in decreased primary CD4+ and CD8+ human T-cell functional responses","volume":"108","author":"Sarin","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_89","doi-asserted-by":"crossref","unstructured":"Di Meglio, P., Di Cesare, A., Laggner, U., Chu, C.C., Napolitano, L., Villanova, F., Tosi, I., Capon, F., Trembath, R.C., and Peris, K. (2011). The IL23R R381Q gene variant protects against immune-mediated diseases by impairing IL-23-induced Th17 effector response in humans. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0017160"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"317","DOI":"10.3109\/1547691X.2014.978056","article-title":"Association between lower frequency of R381Q variant (rs11209026) in IL-23 receptor gene and increased risk of recurrent spontaneous abortion (RSA)","volume":"12","author":"Abdollahi","year":"2015","journal-title":"J. Immunotoxicol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"1062","DOI":"10.4049\/jimmunol.1401850","article-title":"The human IL-23 receptor rs11209026 A allele promotes the expression of a soluble IL-23R-encoding mRNA species","volume":"194","author":"Yu","year":"2015","journal-title":"J. Immunol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"1177","DOI":"10.1093\/ibd\/izaa033","article-title":"Genetic analysis of ulcerative colitis in Japanese individuals using population-specific SNP array","volume":"26","author":"Okamoto","year":"2020","journal-title":"Inflamm. Bowel Dis."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1097\/MIB.0000000000000584","article-title":"Identification of Ten Additional Susceptibility Loci for Ulcerative Colitis Through Immunochip Analysis in Koreans","volume":"22","author":"Ye","year":"2016","journal-title":"Inflamm. Bowel Dis."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1007\/s12041-009-0027-9","article-title":"Contribution of rs11465788 in IL23R gene to Crohn\u2019s disease susceptibility and phenotype in Chinese population","volume":"88","author":"Bin","year":"2009","journal-title":"J. Genet."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1038\/ng.872","article-title":"Extensive genomic and transcriptional diversity identified through massively parallel DNA and RNA sequencing of eighteen Korean individuals","volume":"43","author":"Ju","year":"2011","journal-title":"Nat. Genet."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"156743","DOI":"10.1016\/j.cyto.2024.156743","article-title":"Case-control study of IL23R rs76418789 polymorphism, smoking, and ulcerative colitis in Japan","volume":"183","author":"Miyake","year":"2024","journal-title":"Cytokine"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1038\/ng.733","article-title":"Resequencing of positional candidates identifies low frequency IL23R coding variants protecting against inflammatory bowel disease","volume":"43","author":"Momozawa","year":"2011","journal-title":"Nat. Genet."},{"key":"ref_98","doi-asserted-by":"crossref","unstructured":"Ali, B.R., Ben-Rebeh, I., John, A., Akawi, N.A., Milhem, R.M., Al-Shehhi, N.A., Al-Ameri, M.M., Al-Shamisi, S.A., and Al-Gazali, L. (2011). Endoplasmic reticulum quality control is involved in the mechanism of endoglin-mediated hereditary haemorrhagic telangiectasia. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0026206"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"2871","DOI":"10.1016\/j.bbamcr.2014.08.013","article-title":"Impaired trafficking of the very low density lipoprotein receptor caused by missense mutations associated with dysequilibrium syndrome","volume":"1843","author":"Kizhakkedath","year":"2014","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"26840","DOI":"10.1074\/jbc.M112.355743","article-title":"The amyloid precursor protein copper binding domain histidine residues 149 and 151 mediate APP stability and metabolism","volume":"287","author":"Spoerri","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"21473","DOI":"10.1074\/jbc.R113.481549","article-title":"The multifaceted proprotein convertases: Their unique, redundant, complementary, and opposite functions","volume":"288","author":"Seidah","year":"2013","journal-title":"J. Biol. Chem."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1007\/978-1-61779-204-5_3","article-title":"The proprotein convertases, 20 years later","volume":"768","author":"Seidah","year":"2011","journal-title":"Methods Mol. Biol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"67851","DOI":"10.18632\/oncotarget.12296","article-title":"Analysis of the association of single nucleotide polymorphisms of interleukin-23 receptor (IL-23R) and inflammatory bowel disease in a Chinese Han cohort","volume":"7","author":"Lu","year":"2016","journal-title":"Oncotarget"},{"key":"ref_104","doi-asserted-by":"crossref","unstructured":"Beaudoin, M., Goyette, P., Boucher, G., Lo, K.S., Rivas, M.A., Stevens, C., Alikashani, A., Ladouceur, M., Ellinghaus, D., and Torkvist, L. (2013). Deep resequencing of GWAS loci identifies rare variants in CARD9, IL23R and RNF186 that are associated with ulcerative colitis. PLoS Genet., 9.","DOI":"10.1371\/journal.pgen.1003723"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"E4717","DOI":"10.1073\/pnas.1514230112","article-title":"Biologically active LIL proteins built with minimal chemical diversity","volume":"112","author":"Heim","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"1573","DOI":"10.4049\/jimmunol.1101494","article-title":"Cutting edge: A variant of the IL-23R gene associated with inflammatory bowel disease induces loss of microRNA regulation and enhanced protein production","volume":"188","author":"Zwiers","year":"2012","journal-title":"J. Immunol."},{"key":"ref_107","first-page":"128","article-title":"IL-23 receptor gene rs7517847 and rs1004819 SNPs in ulcerative colitis","volume":"9","author":"Hayatbakhsh","year":"2012","journal-title":"Iran. J. Immunol."},{"key":"ref_108","doi-asserted-by":"crossref","unstructured":"Glas, J., Seiderer, J., Wetzke, M., Konrad, A., T\u00f6r\u00f6k, H.P., Schmechel, S., Tonenchi, L., Grassl, C., Dambacher, J., and Pfennig, S. (2007). rs1004819 is the main disease-associated IL23R variant in German Crohn\u2019s disease patients: Combined analysis of IL23R, CARD15, and OCTN1\/2 variants. PLoS ONE, 2.","DOI":"10.1371\/journal.pone.0000819"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1016\/j.cyto.2013.11.011","article-title":"Marked differences of haplotype tagging SNP distribution, linkage, and haplotype profile of IL23 receptor gene in Roma and Hungarian population samples","volume":"65","author":"Magyari","year":"2014","journal-title":"Cytokine"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"5823","DOI":"10.3748\/wjg.v21.i19.5823","article-title":"Contribution of the IL-17\/IL-23 axis to the pathogenesis of inflammatory bowel disease","volume":"21","author":"Cozma","year":"2015","journal-title":"World J. Gastroenterol."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1038\/s41575-023-00768-1","article-title":"Alimentiv Translational Research Consortium (ATRC) IL-12 and IL-23 pathway inhibition in inflammatory bowel disease","volume":"20","author":"Verstockt","year":"2023","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"ii30","DOI":"10.1093\/ecco-jcc\/jjac011","article-title":"Ustekinumab in Crohn\u2019s Disease: New Data for Positioning in Treatment Algorithm","volume":"16","author":"Danese","year":"2022","journal-title":"J. Crohns Colitis"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1007\/s40259-020-00451-w","article-title":"Clinical Trials of IL-12\/IL-23 Inhibitors in Inflammatory Bowel Disease","volume":"34","author":"Almradi","year":"2020","journal-title":"BioDrugs"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"e13706","DOI":"10.1111\/cts.13706","article-title":"Risankizumab: Mechanism of action, clinical and translational science","volume":"17","author":"Pang","year":"2024","journal-title":"Clin. Transl. Sci."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"581","DOI":"10.2217\/imt-2023-0219","article-title":"Positioning risankizumab in the treatment algorithm of moderate-to-severe Crohn\u2019s disease","volume":"16","author":"Lusetti","year":"2024","journal-title":"Immunotherapy"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1002\/ueg2.12547","article-title":"Difficult-to-treat inflammatory bowel disease: Effectiveness and safety of 4th and 5th lines of treatment","volume":"12","author":"Caron","year":"2024","journal-title":"United Eur. Gastroenterol. J."},{"key":"ref_117","unstructured":"(2023). Risankizumab Induction Therapy in Patients With Moderately to Severely Active Ulcerative Colitis: Efficacy and Safety in the Randomized Phase 3 INSPIRE Study. Gastroenterol. Hepatol., 19, 9\u201310."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1053\/j.gastro.2024.05.036","article-title":"Targeting the Interleukin 23 Pathway in Inflammatory Bowel Disease","volume":"168","author":"Bourgonje","year":"2025","journal-title":"Gastroenterology"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"2444","DOI":"10.1056\/NEJMoa2207940","article-title":"Mirikizumab as Induction and Maintenance Therapy for Ulcerative Colitis","volume":"388","author":"Dubinsky","year":"2023","journal-title":"N. Engl. J. Med."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1053\/j.gastro.2021.10.050","article-title":"Efficacy and Safety of Mirikizumab in a Randomized Phase 2 Study of Patients With Crohn\u2019s Disease","volume":"162","author":"Sands","year":"2022","journal-title":"Gastroenterology"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1007\/s00535-024-02130-x","article-title":"Immunity in digestive diseases: New drugs for inflammatory bowel disease treatment\u2014Insights from Phase II and III trials","volume":"59","author":"Massironi","year":"2024","journal-title":"J. Gastroenterol."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/S2468-1253(23)00318-7","article-title":"Efficacy and safety of 48 weeks of guselkumab for patients with Crohn\u2019s disease: Maintenance results from the phase 2, randomised, double-blind GALAXI-1 trial","volume":"9","author":"Danese","year":"2024","journal-title":"Lancet Gastroenterol. Hepatol."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"1443","DOI":"10.1053\/j.gastro.2023.08.038","article-title":"Guselkumab in Patients With Moderately to Severely Active Ulcerative Colitis: QUASAR Phase 2b Induction Study","volume":"165","author":"Allegretti","year":"2023","journal-title":"Gastroenterology"},{"key":"ref_124","doi-asserted-by":"crossref","unstructured":"Danese, S., Beaton, A., Duncan, E.A., Mercier, A.K., Neisen, J., Seth, H., Zetterstrand, S., and Sands, B.E. (2023). Long-term safety of brazikumab in the open-label period of a randomized phase 2a study of patients with Crohn\u2019s disease. BMC Gastroenterol., 23.","DOI":"10.1186\/s12876-023-03078-7"},{"key":"ref_125","doi-asserted-by":"crossref","unstructured":"Fourie, A.M., Cheng, X., Chang, L., Greving, C., Li, X., Knight, B., Polidori, D., Patrick, A., Bains, T., and Steele, R. (2024). JNJ-77242113, a highly potent, selective peptide targeting the IL-23 receptor, provides robust IL-23 pathway inhibition upon oral dosing in rats and humans. Sci. Rep., 14.","DOI":"10.1038\/s41598-024-67371-5"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1111\/jpc.16519","article-title":"Novel pharmacological developments in the management of paediatric inflammatory bowel disease: Time for guideline update\u2014A narrative review","volume":"60","author":"Lee","year":"2024","journal-title":"J. Paediatr. Child. Health"},{"key":"ref_127","first-page":"46","article-title":"[Pregnancy and breastfeeding in Crohn\u2019s disease]","volume":"149","author":"Sonnenberg","year":"2024","journal-title":"Dtsch. Med. Wochenschr."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"1018","DOI":"10.1007\/s10620-021-06932-4","article-title":"Effectiveness and Safety of Ustekinumab in Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis","volume":"67","author":"Honap","year":"2022","journal-title":"Dig Dis Sci."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1111\/apt.17751","article-title":"Clinical trial: Clinical and endoscopic outcomes with ustekinumab in patients with Crohn\u2019s disease: Results from the long-term extension period of STARDUST","volume":"59","author":"Vermeire","year":"2024","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"2245","DOI":"10.1093\/ibd\/izae024","article-title":"Two-Year Efficacy and Safety of Mirikizumab Following 104 Weeks of Continuous Treatment for Ulcerative Colitis: Results From the LUCENT-3 Open-Label Extension Study","volume":"30","author":"Sands","year":"2024","journal-title":"Inflamm. Bowel Dis."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"2449","DOI":"10.1093\/ibd\/izae133","article-title":"Baseline Assessment of Serum Cytokines Predicts Clinical and Endoscopic Response to Ustekinumab in Patients With Crohn\u2019s Disease: A Prospective Pilot Study","volume":"30","author":"Bertani","year":"2024","journal-title":"Inflamm. Bowel Dis."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"jjaf006","DOI":"10.1093\/ecco-jcc\/jjaf006","article-title":"Improvement in serum eosinophilia is observed in clinical responders to ustekinumab but not adalimumab in inflammatory bowel disease","volume":"19","author":"Wong","year":"2025","journal-title":"J. Crohns Colitis"},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1089\/cell.2018.0006","article-title":"Genetically Engineered Adipose Mesenchymal Stem Cells Using HIV-Based Lentiviral Vectors as Gene Therapy for Autoimmune Diseases","volume":"20","author":"Rostami","year":"2018","journal-title":"Cell Reprogram."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/10\/4775\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:33:51Z","timestamp":1760031231000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/10\/4775"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,16]]},"references-count":133,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2025,5]]}},"alternative-id":["ijms26104775"],"URL":"https:\/\/doi.org\/10.3390\/ijms26104775","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5,16]]}}}