{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T09:34:12Z","timestamp":1792056852454,"version":"4.4.0"},"reference-count":63,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,9,6]],"date-time":"2024-09-06T00:00:00Z","timestamp":1725580800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000072","name":"National Institute of Dental and Craniofacial Research","doi-asserted-by":"publisher","award":["R01DE29472"],"award-info":[{"award-number":["R01DE29472"]}],"id":[{"id":"10.13039\/100000072","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006108","name":"National Center for Advancing Translational Sciences","doi-asserted-by":"publisher","award":["UL1TR001412"],"award-info":[{"award-number":["UL1TR001412"]}],"id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell Dev. Biol."],"abstract":"<jats:p>Primary Sj\u00f6gren\u2019s disease (pSD) is a systemic autoimmune disease that has the strongest female predilection of all autoimmune diseases. The underlying mechanisms that govern this sexual dimorphism, however, remain poorly understood. We hypothesized that pSD females would exhibit more robust disease as compared to males, and that Tlr7 controls distinct disease manifestations in males and females. Using a well-established pSD mouse model, we harvested exocrine glands, and pulmonary and renal tissue from males and females and quantified the inflammation present. We then collected salivary glands, spleens, and cervical lymph nodes and performed flow cytometry to assess immune populations implicated in disease. We also harvested sera to examine total and autoreactive antibodies. Our data revealed that pSD mice displayed sex-biased disease, as pSD females showed decreased dacryoadenitis, but increased nephritis as compared to males. Moreover, females exhibited increased proportions of germinal center B cells and CD4<jats:sup>+<\/jats:sup> activated\/memory T cells in the periphery. Additionally, salivary gland immune populations were altered in a sex-dependent manner in pSD. Females with pSD also displayed elevated total and autoreactive IgG as compared to males. Additionally, splenic B cell Tlr7 expression was increased in females. We next generated pSD mice that lacked <jats:italic>Tlr7<\/jats:italic> systemically and found that ablation of Tlr<jats:italic>7<\/jats:italic> was primarily protective in pSD females, while Tlr7-deficient pSD males showed heightened disease. Thus, pSD mice display sex-biased disease and these dichotomous manifestations are governed by Tlr7 activation. This study identifies Tlr7 as a druggable target for pSD, and highlights the importance of studying pSD disease mechanisms in both sexes.<\/jats:p>","DOI":"10.3389\/fcell.2024.1434269","type":"journal-article","created":{"date-parts":[[2024,9,6]],"date-time":"2024-09-06T09:43:28Z","timestamp":1725615808000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":7,"title":["Tlr7 drives sex- and tissue-dependent effects in Sj\u00f6gren\u2019s disease"],"prefix":"10.3389","volume":"12","author":[{"given":"Achamaporn","family":"Punnanitinont","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheta","family":"Biswas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eileen M.","family":"Kasperek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason","family":"Osinski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chengsong","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey C.","family":"Miecznikowski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rose-Anne","family":"Romano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jill M.","family":"Kramer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,9,6]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"17969","DOI":"10.1038\/s41598-019-54410-9","article-title":"Hyperglycemia and salivary gland dysfunction in the non-obese diabetic mouse: caveats for preclinical studies in Sjogren's syndrome","volume":"9","author":"Allushi","year":"2019","journal-title":"Sci. Rep."},{"key":"B2","doi-asserted-by":"publisher","first-page":"1165","DOI":"10.1214\/aos\/1013699998","article-title":"The control of the false discovery rate in multiple testing under dependency","volume":"29","author":"Benjamini","year":"2001","journal-title":"Ann. Statistics"},{"key":"B3","doi-asserted-by":"publisher","first-page":"958670","DOI":"10.3389\/fmed.2022.958670","article-title":"Sex differences in comorbidities associated with Sjogren's disease","volume":"9","author":"Bruno","year":"2022","journal-title":"Front. Med. (Lausanne)"},{"key":"B4","doi-asserted-by":"publisher","first-page":"315","DOI":"10.1146\/annurev-immunol-092419-031130","article-title":"Age-associated B cells","volume":"38","author":"Cancro","year":"2020","journal-title":"Annu. Rev. Immunol."},{"key":"B5","doi-asserted-by":"publisher","first-page":"e172219","DOI":"10.1172\/jci.insight.172219","article-title":"B cell-intrinsic TLR7 expression drives severe lupus in TLR9-deficient mice","volume":"8","author":"Cosgrove","year":"2023","journal-title":"JCI Insight"},{"key":"B6","doi-asserted-by":"publisher","first-page":"801","DOI":"10.1016\/j.immuni.2007.09.009","article-title":"Control of toll-like receptor 7 expression is essential to restrict autoimmunity and dendritic cell proliferation","volume":"27","author":"Deane","year":"2007","journal-title":"Immunity"},{"key":"B7","doi-asserted-by":"publisher","first-page":"9478","DOI":"10.3390\/ijms21249478","article-title":"Toll-like receptor 7 is required for lacrimal gland autoimmunity and type 1 diabetes development in male nonobese diabetic mice","volume":"21","author":"Debreceni","year":"2020","journal-title":"Int. J. Mol. Sci."},{"key":"B8","doi-asserted-by":"publisher","first-page":"3651","DOI":"10.1172\/JCI42081","article-title":"TLR8 deficiency leads to autoimmunity in mice","volume":"120","author":"Demaria","year":"2010","journal-title":"J. Clin. Invest."},{"key":"B9","doi-asserted-by":"publisher","first-page":"302","DOI":"10.1177\/0961203311425522","article-title":"TLR7\/8\/9 polymorphisms and their associations in systemic lupus erythematosus patients from southern Brazil","volume":"21","author":"dos Santos","year":"2012","journal-title":"Lupus."},{"key":"B10","doi-asserted-by":"publisher","first-page":"2005","DOI":"10.3201\/eid1011.040367","article-title":"Women and autoimmune diseases","volume":"10","author":"Fairweather","year":"2004","journal-title":"Emerg. Infect. Dis."},{"key":"B11","doi-asserted-by":"publisher","first-page":"98","DOI":"10.1038\/s41584-020-00544-4","article-title":"Toll-like receptor signalling in B cells during systemic lupus erythematosus","volume":"17","author":"Fillatreau","year":"2021","journal-title":"Nat. Rev. Rheumatol."},{"key":"B12","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1016\/j.immuni.2011.05.010","article-title":"Unc93B1 restricts systemic lethal inflammation by orchestrating Toll-like receptor 7 and 9 trafficking","volume":"35","author":"Fukui","year":"2011","journal-title":"Immunity"},{"key":"B13","doi-asserted-by":"publisher","first-page":"108485","DOI":"10.1016\/j.celrep.2020.108485","article-title":"Heterogeneous escape from X chromosome inactivation results in sex differences in type I IFN responses at the single human pDC level","volume":"33","author":"Hagen","year":"2020","journal-title":"Cell Rep."},{"key":"B14","doi-asserted-by":"publisher","first-page":"196","DOI":"10.1038\/ni758","article-title":"Small anti-viral compounds activate immune cells via the TLR7 MyD88-dependent signaling pathway","volume":"3","author":"Hemmi","year":"2002","journal-title":"Nat. Immunol."},{"key":"B15","doi-asserted-by":"publisher","first-page":"e20211487","DOI":"10.1084\/jem.20211487","article-title":"The X in seX-biased immunity and autoimmune rheumatic disease","volume":"219","author":"Jiwrajka","year":"2022","journal-title":"J. Exp. Med."},{"key":"B16","doi-asserted-by":"publisher","first-page":"3988","DOI":"10.1074\/jbc.M707264200","article-title":"MyD88 functions as a negative regulator of TLR3\/TRIF-induced corneal inflammation by inhibiting activation of c-Jun N-terminal kinase","volume":"283","author":"Johnson","year":"2008","journal-title":"J. Biol. Chem."},{"key":"B17","doi-asserted-by":"publisher","first-page":"102608","DOI":"10.1016\/j.jaut.2021.102608","article-title":"Tissue-specific activation of Myd88-dependent pathways governs disease severity in primary Sjogren's syndrome","volume":"118","author":"Kiripolsky","year":"2021","journal-title":"J. Autoimmun."},{"key":"B18","doi-asserted-by":"publisher","first-page":"1411","DOI":"10.1189\/jlb.3A0717-311R","article-title":"Myd88 is required for disease development in a primary Sjogren's syndrome mouse model","volume":"102","author":"Kiripolsky","year":"","journal-title":"J. Leukoc. Biol."},{"key":"B19","doi-asserted-by":"publisher","first-page":"2963","DOI":"10.3389\/fimmu.2019.02963","article-title":"Activation of Myd88-dependent TLRs mediates local and systemic inflammation in a mouse model of primary Sjogren\u2019s syndrome","volume":"10","author":"Kiripolsky","year":"2020","journal-title":"Front. Immunol."},{"key":"B20","doi-asserted-by":"publisher","first-page":"225","DOI":"10.1016\/j.clim.2017.04.009","article-title":"Systemic manifestations of primary Sjogren's syndrome in the NOD.B10Sn-H2b\/J mouse model","volume":"183","author":"Kiripolsky","year":"","journal-title":"Clin. Immunol."},{"key":"B21","doi-asserted-by":"publisher","first-page":"1927","DOI":"10.1007\/s10067-024-06955-y","article-title":"Male patients with primary Sjogren's syndrome have unique clinical manifestations and circulating lymphocyte profiles","volume":"43","author":"Liu","year":"2024","journal-title":"Clin. Rheumatol."},{"key":"B22","doi-asserted-by":"publisher","first-page":"366","DOI":"10.1038\/s41586-019-1612-6","article-title":"UNC93B1 recruits syntenin-1 to dampen TLR7 signalling and prevent autoimmunity","volume":"575","author":"Majer","year":"2019","journal-title":"Nature"},{"key":"B23","doi-asserted-by":"publisher","first-page":"e112100","DOI":"10.1371\/journal.pone.0112100","article-title":"Impaired clearance of early apoptotic cells mediated by inhibitory IgG antibodies in patients with primary Sjogren's syndrome","volume":"9","author":"Manoussakis","year":"2014","journal-title":"PLoS One"},{"key":"B24","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1056\/NEJMc1804598","article-title":"Primary Sjogren\u2019s syndrome","volume":"379","author":"Mariette","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"B25","doi-asserted-by":"publisher","first-page":"1011125","DOI":"10.3389\/fimmu.2022.1011125","article-title":"Spatial transcriptomics of the lacrimal gland features macrophage activity and epithelium metabolism as key alterations during chronic inflammation","volume":"13","author":"Mauduit","year":"2022","journal-title":"Front. Immunol."},{"key":"B26","doi-asserted-by":"publisher","first-page":"3385","DOI":"10.4049\/jimmunol.171.7.3385","article-title":"IFN-alpha skews monocyte differentiation into Toll-like receptor 7-expressing dendritic cells with potent functional activities","volume":"171","author":"Mohty","year":"2003","journal-title":"J. Immunol."},{"key":"B27","doi-asserted-by":"publisher","first-page":"1109","DOI":"10.1002\/art.42844","article-title":"Amplified type I interferon response in Sjogren\u2019s disease via ectopic toll-like receptor 7 expression in salivary gland epithelial cells induced by lysosome-associated Membrane protein 3","volume":"76","author":"Nakamura","year":"2024","journal-title":"Arthritis Rheumatol."},{"key":"B28","doi-asserted-by":"publisher","first-page":"876","DOI":"10.1093\/rheumatology\/keq001","article-title":"Up-regulation of the endoplasmic reticulum transmembrane protein UNC93B in the B cells of patients with active systemic lupus erythematosus","volume":"49","author":"Nakano","year":"2010","journal-title":"Rheumatol. Oxf."},{"key":"B29","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1615\/CritRevImmunol.2016018175","article-title":"Natural IgM and the development of B cell-mediated autoimmune diseases","volume":"36","author":"Nguyen","year":"2016","journal-title":"Crit. Rev. Immunol."},{"key":"B30","doi-asserted-by":"publisher","first-page":"1840","DOI":"10.4049\/jimmunol.0902592","article-title":"TLR9 regulates TLR7-and MyD88-dependent autoantibody production and disease in a murine model of lupus","volume":"184","author":"Nickerson","year":"2010","journal-title":"J. Immunol."},{"key":"B31","doi-asserted-by":"publisher","first-page":"2504","DOI":"10.4049\/jimmunol.1402425","article-title":"Cell-intrinsic expression of TLR9 in autoreactive B cells constrains BCR\/TLR7-dependent responses","volume":"194","author":"Nundel","year":"2015","journal-title":"J. Immunol."},{"key":"B32","doi-asserted-by":"publisher","first-page":"606268","DOI":"10.3389\/fimmu.2020.606268","article-title":"Transcriptomic and network analysis of minor salivary glands of patients with primary Sjogren\u2019s syndrome","volume":"11","author":"Oyelakin","year":"2020","journal-title":"Front. Immunol."},{"key":"B33","doi-asserted-by":"publisher","first-page":"1388","DOI":"10.1111\/1756-185X.13940","article-title":"Male patients with primary Sjogren\u2019s syndrome: a distinct clinical subgroup?","volume":"23","author":"Park","year":"2020","journal-title":"Int. J. Rheum. Dis."},{"key":"B34","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1111\/imr.13068","article-title":"Molecular mechanisms controlling age-associated B cells in autoimmunity","volume":"307","author":"Phalke","year":"2022","journal-title":"Immunol. Rev."},{"key":"B35","doi-asserted-by":"publisher","first-page":"1669","DOI":"10.1126\/science.1124978","article-title":"Autoreactive B cell responses to RNA-related antigens due to TLR7 gene duplication","volume":"312","author":"Pisitkun","year":"2006","journal-title":"Science"},{"key":"B36","doi-asserted-by":"publisher","first-page":"1034336","DOI":"10.3389\/fimmu.2022.1034336","article-title":"TLR7 agonism accelerates disease in a mouse model of primary Sjogren's syndrome and drives expansion of T-bet(+) B cells","volume":"13","author":"Punnanitinont","year":"2022","journal-title":"Front. Immunol."},{"key":"B37","doi-asserted-by":"publisher","first-page":"497","DOI":"10.1093\/jleuko\/qiad135","article-title":"TLR7 activation of age-associated B cells mediates disease in a mouse model of primary Sjogren's disease","volume":"115","author":"Punnanitinont","year":"2024","journal-title":"J. Leukoc. Biol."},{"key":"B38","doi-asserted-by":"publisher","first-page":"1168645","DOI":"10.3389\/fdmed.2023.1168645","article-title":"Sex-specific differences in primary Sjogren's disease","volume":"4","author":"Punnanitinont","year":"2023","journal-title":"Front. Dent. Med."},{"key":"B39","doi-asserted-by":"publisher","first-page":"e20232005","DOI":"10.1084\/jem.20232005","article-title":"Large-scale mutational analysis identifies UNC93B1 variants that drive TLR-mediated autoimmunity in mice and humans","volume":"221","author":"Rael","year":"2024","journal-title":"J. Exp. Med."},{"key":"B40","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1186\/s13293-017-0137-7","article-title":"Difference in clinical presentation between women and men in incident primary Sjogren's syndrome","volume":"8","author":"Ramirez Sepulveda","year":"2017","journal-title":"Biol. Sex. Differ."},{"key":"B41","doi-asserted-by":"publisher","first-page":"4813","DOI":"10.1038\/s41467-021-25102-8","article-title":"Altered function and differentiation of age-associated B cells contribute to the female bias in lupus mice","volume":"12","author":"Ricker","year":"2021","journal-title":"Nat. Commun."},{"key":"B42","doi-asserted-by":"publisher","first-page":"150","DOI":"10.1002\/1529-0131(199801)41:1<150::AID-ART18>3.0.CO;2-T","article-title":"A novel NOD-derived murine model of primary Sjogren's syndrome","volume":"41","author":"Robinson","year":"1998","journal-title":"Arthritis Rheum."},{"key":"B43","doi-asserted-by":"publisher","first-page":"1305","DOI":"10.1182\/blood-2011-01-331462","article-title":"Toll-like receptor 7 (TLR7)-driven accumulation of a novel CD11c\u207a B-cell population is important for the development of autoimmunity","volume":"118","author":"Rubtsov","year":"2011","journal-title":"Blood"},{"key":"B44","doi-asserted-by":"publisher","first-page":"210","DOI":"10.1007\/s12026-012-8365-8","article-title":"TLR7 drives accumulation of ABCs and autoantibody production in autoimmune-prone mice","volume":"55","author":"Rubtsov","year":"2013","journal-title":"Immunol. Res."},{"key":"B45","doi-asserted-by":"publisher","first-page":"80","DOI":"10.1007\/s11926-021-01047-1","article-title":"TLR7 signaling in lupus B cells: new insights into synergizing factors and downstream signals","volume":"23","author":"Satterthwaite","year":"2021","journal-title":"Curr. Rheumatol. Rep."},{"key":"B46","doi-asserted-by":"publisher","first-page":"6208","DOI":"10.4049\/jimmunol.178.10.6208","article-title":"Sensitization to TLR7 agonist in IFN-beta-preactivated dendritic cells","volume":"178","author":"Severa","year":"2007","journal-title":"J. Immunol."},{"key":"B47","doi-asserted-by":"publisher","first-page":"15838","DOI":"10.1073\/pnas.1001337107","article-title":"Sex-specific association of X-linked Toll-like receptor 7 (TLR7) with male systemic lupus erythematosus","volume":"107","author":"Shen","year":"2010","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"B48","doi-asserted-by":"publisher","first-page":"4400","DOI":"10.4049\/jimmunol.1401720","article-title":"B cell-intrinsic TLR7 signaling is essential for the development of spontaneous germinal centers","volume":"193","author":"Soni","year":"2014","journal-title":"J. Immunol."},{"key":"B49","doi-asserted-by":"publisher","first-page":"eaap8855","DOI":"10.1126\/sciimmunol.aap8855","article-title":"TLR7 escapes X chromosome inactivation in immune cells","volume":"3","author":"Souyris","year":"2018","journal-title":"Sci. Immunol."},{"key":"B50","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1007\/s00281-018-0712-y","article-title":"Female predisposition to TLR7-driven autoimmunity: gene dosage and the escape from X chromosome inactivation","volume":"41","author":"Souyris","year":"2019","journal-title":"Semin. Immunopathol."},{"key":"B51","doi-asserted-by":"publisher","first-page":"443","DOI":"10.3109\/08830185.2014.921164","article-title":"TLR cross-talk confers specificity to innate immunity","volume":"33","author":"Tan","year":"2014","journal-title":"Int. Rev. Immunol."},{"key":"B52","doi-asserted-by":"publisher","first-page":"288","DOI":"10.1038\/s41584-023-00932-6","article-title":"Genetics and epigenetics of primary Sjogren syndrome: implications for future therapies","volume":"19","author":"Thorlacius","year":"2023","journal-title":"Nat. Rev. Rheumatol."},{"key":"B53","doi-asserted-by":"publisher","first-page":"3172","DOI":"10.1172\/JCI132328","article-title":"B cell-intrinsic TLR9 expression is protective in murine lupus","volume":"130","author":"Tilstra","year":"2020","journal-title":"J. Clin. Invest."},{"key":"B54","doi-asserted-by":"publisher","first-page":"681941","DOI":"10.3389\/fimmu.2021.681941","article-title":"The transcriptome of paired major and minor salivary gland tissue in patients with primary Sjogren\u2019s syndrome","volume":"12","author":"Verstappen","year":"2021","journal-title":"Front. Immunol."},{"key":"B55","doi-asserted-by":"publisher","first-page":"478","DOI":"10.1126\/science.adg6427","article-title":"Innate virus-sensing pathways in B cell systemic autoimmunity","volume":"380","author":"Vinuesa","year":"2023","journal-title":"Science"},{"key":"B56","doi-asserted-by":"publisher","first-page":"3792","DOI":"10.1038\/srep03792","article-title":"Genetic variations in Toll-like receptors (TLRs 3\/7\/8) are associated with systemic lupus erythematosus in a Taiwanese population","volume":"4","author":"Wang","year":"2014","journal-title":"Sci. Rep."},{"key":"B57","doi-asserted-by":"publisher","first-page":"676010","DOI":"10.3389\/fimmu.2021.676010","article-title":"TLR7 signaling drives the development of Sjogren\u2019s syndrome","volume":"12","author":"Wang","year":"2021","journal-title":"Front. Immunol."},{"key":"B58","doi-asserted-by":"publisher","first-page":"9711","DOI":"10.3390\/ijms22189711","article-title":"Defective efferocytosis in a murine model of Sjogren\u2019s syndrome is mediated by dysfunctional mer tyrosine kinase receptor","volume":"22","author":"Witas","year":"2021","journal-title":"Int. J. Mol. Sci."},{"key":"B59","doi-asserted-by":"publisher","first-page":"8593","DOI":"10.1038\/s41598-022-12608-4","article-title":"Bone marrow-derived macrophages from a murine model of Sjogren's syndrome demonstrate an aberrant, inflammatory response to apoptotic cells","volume":"12","author":"Witas","year":"2022","journal-title":"Sci. Rep."},{"key":"B60","doi-asserted-by":"publisher","first-page":"eadi9769","DOI":"10.1126\/sciimmunol.adi9769","article-title":"UNC93B1 variants underlie TLR7-dependent autoimmunity","volume":"9","author":"Wolf","year":"2024","journal-title":"Sci. Immunol."},{"key":"B61","doi-asserted-by":"publisher","first-page":"867","DOI":"10.1016\/j.immuni.2012.07.018","article-title":"Nucleic acid-sensing Toll-like receptors are essential for the control of endogenous retrovirus viremia and ERV-induced tumors","volume":"37","author":"Yu","year":"2012","journal-title":"Immunity"},{"key":"B62","doi-asserted-by":"publisher","first-page":"3371","DOI":"10.1016\/j.celrep.2018.11.081","article-title":"Structural analyses of toll-like receptor 7 reveal detailed RNA sequence specificity and recognition mechanism of agonistic ligands","volume":"25","author":"Zhang","year":"2018","journal-title":"Cell Rep."},{"key":"B63","doi-asserted-by":"publisher","first-page":"e667","DOI":"10.1097\/MD.0000000000000667","article-title":"Primary Sjogren syndrome in Han Chinese: clinical and immunological characteristics of 483 patients","volume":"94","author":"Zhao","year":"2015","journal-title":"Med. (Baltimore)"}],"container-title":["Frontiers in Cell and Developmental Biology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcell.2024.1434269\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,9,6]],"date-time":"2024-09-06T09:43:32Z","timestamp":1725615812000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcell.2024.1434269\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,9,6]]},"references-count":63,"alternative-id":["10.3389\/fcell.2024.1434269"],"URL":"https:\/\/doi.org\/10.3389\/fcell.2024.1434269","relation":{},"ISSN":["2296-634X"],"issn-type":[{"value":"2296-634X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,9,6]]},"article-number":"1434269"}}