CXCL13/CXCR5 chemokine axis promotes antiviral CXCR5+CD19+ B Cells and follicular/effector CXCR5+CD4+ T Cells in the lungs associated with protection from severe and fatal COVID-19 following infection with pathogenic SARS-CoV-2 Delta variant

DOI record: { "DOI": "10.1093/jimmun/vkag017", "ISSN": [ "0022-1767", "1550-6606" ], "URL": "http://dx.doi.org/10.1093/jimmun/vkag017", "abstract": "<jats:title>Abstract</jats:title>\n <jats:p>Chemokines play a crucial role in the lung’s immune responses to infections and diseases. The role of CXC ligand 13 (CXCL13), a chemokine produced homeostatically by various lung cell types, in protecting against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and disease remains controversial. Some studies reported that patients who survived severe coronavirus disease 2019 (COVID-19) had CXCL13-dominated lung immune responses early in infection. In contrast, other studies reported that high CXCL13 levels were associated with severe COVID-19. In this study, to determine the direct role of CXCL13 in SARS-CoV-2 infection and disease, we generated CXCL13−/−K18-hACE2 mice, that are both transgenic for ACE2 and deficient in CXCL13, and compared their infection and COVID-19-like symptoms with those in wild-type K18-hACE2 transgenic mouse littermates following intranasal inoculation with the pathogenic SARS-CoV-2 delta variant (B.1.617.2). Compared to age- and gender-matched SARS-CoV-2 infected wild-type K18-hACE2 mice, the SARS-CoV-2 infected CXCL13−/−K18-hACE2 deficient mice exhibited (i) higher viral load in the lungs; (ii) severe COVID-19-like lung pathology; (iii) exacerbated weight loss; and (iv) increased mortality. The apparent severe COVID-19-like symptoms in CXCL13−/−K18-hACE2 deficient mice were associated with: (i) significantly lower frequencies of functional lung-resident C-X-C chemokine receptor 5+ (CXCR5)+CD19+ B-cells, follicular CXCR5+CD4+ helper T cells (Tfh cells), and effector IFN-γ+TNF-α+GzmB+Ki67+ CD4+ Th1 cells; and (ii) a significant reduction in the levels of SARS-CoV-2-Spike specific IgG1 and IgG2b antibody isotypes. These findings corroborate previous human reports suggesting a protective role for the CXCL13/CXCR5 chemokine axis in combating SARS-CoV-2 infection and disease by promoting B cell- and T cell-mediated immunity, offering a potential new immunotherapeutic target.</jats:p>", "article-number": "vkag017", "author": [ { "affiliation": [ { "name": "Laboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, University of California Irvine, School of Medicine , Irvine, CA,", "place": [ "United States" ] }, { "name": "Department of Vaccines and Immunotherapies, TechImmune, LLC, University Lab Partners , Irvine, CA,", "place": [ "United States" ] } ], "family": "Vahed", "given": "Hawa", "sequence": "first" }, { "affiliation": [ { "name": "Laboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, University of California Irvine, School of Medicine , Irvine, CA,", "place": [ "United States" ] } ], "family": "Chentoufi", "given": "Aziz A", "sequence": "additional" }, { "affiliation": [ { "name": "Laboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, University of California Irvine, School of Medicine , Irvine, CA,", "place": [ "United States" ] } ], "family": "Prakash", "given": "Swayam", "sequence": "additional" }, { "affiliation": [ { "name": "Laboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, University of California Irvine, School of Medicine , Irvine, CA,", "place": [ "United States" ] } ], "family": "Quadiri", "given": "Afshana", "sequence": "additional" }, { "affiliation": [ { "name": "Laboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, University of California Irvine, School of Medicine , Irvine, CA,", "place": [ "United States" ] } ], "family": "Karan", "given": "Sweta", "sequence": "additional" }, { "affiliation": [ { "name": "Laboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, University of California Irvine, School of Medicine , Irvine, CA,", "place": [ "United States" ] } ], "family": "Lekbach", "given": "Yassir", "sequence": "additional" }, { "affiliation": [ { "name": "Laboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, University of California Irvine, School of Medicine , Irvine, CA,", "place": [ "United States" ] } ], "family": "Omorogieva", "given": "Etinosa", "sequence": "additional" }, { "affiliation": [ { "name": "Laboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, University of California Irvine, School of Medicine , Irvine, CA,", "place": [ "United States" ] } ], "family": "Patel", "given": "Swena", "sequence": "additional" }, { "affiliation": [ { "name": "Laboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, University of California Irvine, School of Medicine , Irvine, CA,", "place": [ "United States" ] } ], "family": "Tadros", "given": "Jimmy", "sequence": "additional" }, { "affiliation": [ { "name": "Laboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, University of California Irvine, School of Medicine , Irvine, CA,", "place": [ "United States" ] } ], "family": "Liao", "given": "Emma Jane", "sequence": "additional" }, { "affiliation": [ { "name": "Laboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, University of California Irvine, School of Medicine , Irvine, CA,", "place": [ "United States" ] } ], "family": "Lau", "given": "Lauren", "sequence": "additional" }, { "affiliation": [ { "name": "Department of Pathology and Laboratory Medicine, School of Medicine, University of California Irvine , Irvine, CA,", "place": [ "United States" ] } ], "family": "Tifrea", "given": "Delia F", "sequence": "additional" }, { "affiliation": [ { "name": "Department of Molecular Biology & Biochemistry, University of California Irvine, School of Medicine , Irvine, CA,", "place": [ "United States" ] }, { "name": "High containment facility, University of California Irvine, School of Medicine , Irvine, CA,", "place": [ "United States" ] } ], "family": "Ibraim", "given": "Izabela Coimbra", "sequence": "additional" }, { "affiliation": [ { "name": "Laboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, University of California Irvine, School of Medicine , Irvine, CA,", "place": [ "United States" ] }, { "name": "Department of Vaccines and Immunotherapies, TechImmune, LLC, University Lab Partners , Irvine, CA,", "place": [ "United States" ] }, { "name": "Institute for Immunology, University of California Irvine, School of Medicine , Irvine, CA,", "place": [ "United States" ] } ], "family": "BenMohamed", "given": "Lbachir", "sequence": "additional" } ], "container-title": "The Journal of Immunology", "content-domain": { "crossmark-restriction": false, "domain": [] }, "created": { "date-parts": [ [ 2026, 3, 18 ] ], "date-time": "2026-03-18T09:56:26Z", "timestamp": 1773827786000 }, "deposited": { "date-parts": [ [ 2026, 3, 18 ] ], "date-time": "2026-03-18T09:56:36Z", "timestamp": 1773827796000 }, "funder": [ { "award": [ "AI158060" ], "award-info": [ { "award-number": [ "AI158060" ] } ], "name": "Public Health Service Research" }, { "award": [ "AI150091" ], "award-info": [ { "award-number": [ "AI150091" ] } ], "name": "Public Health Service Research" }, { "award": [ "AI143348" ], "award-info": [ { "award-number": [ "AI143348" ] } ], "name": "Public Health Service Research" }, { "award": [ "AI147499" ], "award-info": [ { "award-number": [ "AI147499" ] } ], "name": "Public Health Service Research" }, { "award": [ "AI143326" ], "award-info": [ { "award-number": [ "AI143326" ] } ], "name": "Public Health Service Research" }, { "award": [ "AI138764" ], "award-info": [ { "award-number": [ "AI138764" ] } ], "name": "Public Health Service Research" }, { "award": [ "AI124911" ], "award-info": [ { "award-number": [ "AI124911" ] } ], "name": "Public Health Service Research" }, { "award": [ "AI110902" ], "award-info": [ { "award-number": [ "AI110902" ] } ], "name": "Public Health Service Research" }, { "DOI": "10.13039/100000060", "doi-asserted-by": "crossref", "id": [ { "asserted-by": "crossref", "id": "10.13039/100000060", "id-type": "DOI" } ], "name": "National Institute of Allergy and Infectious Diseases" } ], "indexed": { "date-parts": [ [ 2026, 3, 18 ] ], "date-time": "2026-03-18T15:21:30Z", "timestamp": 1773847290552, "version": "3.50.1" }, "is-referenced-by-count": 0, "issue": "3", "issued": { "date-parts": [ [ 2026, 3 ] ] }, "journal-issue": { "issue": "3", "published-print": { "date-parts": [ [ 2026, 3, 17 ] ] } }, "language": "en", "license": [ { "URL": "https://creativecommons.org/licenses/by-nc/4.0/", "content-version": "vor", "delay-in-days": 17, "start": { "date-parts": [ [ 2026, 3, 18 ] ], "date-time": "2026-03-18T00:00:00Z", "timestamp": 1773792000000 } } ], "link": [ { "URL": "https://academic.oup.com/jimmunol/article-pdf/215/3/vkag017/67387273/vkag017.pdf", "content-type": "application/pdf", "content-version": "vor", "intended-application": "syndication" }, { "URL": "https://academic.oup.com/jimmunol/article-pdf/215/3/vkag017/67387273/vkag017.pdf", "content-type": "unspecified", "content-version": "vor", "intended-application": "similarity-checking" } ], "member": "286", "original-title": [], "prefix": "10.1093", "published": { "date-parts": [ [ 2026, 3 ] ] }, "published-online": { "date-parts": [ [ 2026, 3, 18 ] ] }, "published-other": { "date-parts": [ [ 2026, 3 ] ] }, "published-print": { "date-parts": [ [ 2026, 3, 17 ] ] }, "publisher": "Oxford University Press (OUP)", "reference": [ { "DOI": "10.1016/j.ijbiomac.2024.136233", "article-title": "Optimized aptamer-based next generation biosensor for the ultra-sensitive determination of SARS-CoV-2 S1 protein in saliva samples", "author": "Erdem", "doi-asserted-by": "crossref", "first-page": "136233", "journal-title": "Int J Biol Macromol", "key": "2026031805360758600_vkag017-B1", "volume": "281", "year": "2024" }, { "DOI": "10.1038/s41598-024-71419-x", "article-title": "Immunologic mediators profile in COVID-19 convalescence", "author": "Silva-Junior", "doi-asserted-by": "crossref", "first-page": "20930", "journal-title": "Sci Rep", "key": "2026031805360758600_vkag017-B2", "volume": "14", "year": "2024" }, { "DOI": "10.1186/s13690-021-00779-x", "article-title": "COVID-19 denial in Turkmenistan veiling the real situation", "author": "Hashim", "doi-asserted-by": "crossref", "first-page": "8", "journal-title": "Arch Public Health", "key": "2026031805360758600_vkag017-B3", "volume": "80", "year": "2022" }, { "DOI": "10.1016/j.biopha.2020.110499", "article-title": "Outbreak of COVID-19: an emerging global pandemic threat", "author": "Peng", "doi-asserted-by": "crossref", "first-page": "110499", "journal-title": "Biomed Pharmacother", "key": "2026031805360758600_vkag017-B4", "volume": "129", "year": "2020" }, { "DOI": "10.1007/s11357-024-01379-7", "article-title": "Creating respiratory pathogen-free environments in healthcare and nursing-care settings: a comprehensive review", "author": "Nagy", "doi-asserted-by": "crossref", "first-page": "543", "journal-title": "Geroscience", "key": "2026031805360758600_vkag017-B5", "volume": "47", "year": "2025" }, { "author": "Aleem", "key": "2026031805360758600_vkag017-B6", "year": "2024" }, { "DOI": "10.3389/fimmu.2024.1343716", "article-title": "High frequencies of alpha common cold coronavirus/SARS-CoV-2 cross-reactive functional CD4(+) and CD8(+) memory T cells are associated with protection from symptomatic and fatal SARS-CoV-2 infections in unvaccinated COVID-19 patients", "author": "Coulon", "doi-asserted-by": "crossref", "first-page": "1343716", "journal-title": "Front Immunol", "key": "2026031805360758600_vkag017-B7", "volume": "15", "year": "2024" }, { "first-page": "1328905", "key": "2026031805360758600_vkag017-B8", "year": "2024" }, { "DOI": "10.4049/jimmunol.2001438", "article-title": "Genome-wide B Cell, CD4(+), and CD8(+) T cell epitopes that are highly conserved between human and animal coronaviruses, identified from SARS-CoV-2 as targets for preemptive pan-coronavirus vaccines", "author": "Prakash", "doi-asserted-by": "crossref", "first-page": "2566", "journal-title": "J Immunol", "key": "2026031805360758600_vkag017-B9", "volume": "206", "year": "2021" }, { "DOI": "10.1172/JCI137647", "article-title": "SARS-CoV-2: a storm is raging", "author": "Pedersen", "doi-asserted-by": "crossref", "first-page": "2202", "journal-title": "J Clin Invest", "key": "2026031805360758600_vkag017-B10", "volume": "130", "year": "2020" }, { "DOI": "10.1016/j.cytogfr.2023.11.005", "article-title": "COVID-19: from emerging variants to vaccination", "author": "Senevirathne", "doi-asserted-by": "crossref", "first-page": "127", "journal-title": "Cytokine Growth Factor Rev", "key": "2026031805360758600_vkag017-B11", "volume": "76", "year": "2024" }, { "article-title": "Loss of smell or taste as the only symptom of COVID-19", "author": "Hjelmesæth", "journal-title": "Tidsskr Nor Laegeforen", "key": "2026031805360758600_vkag017-B12", "volume": "140", "year": "2020" }, { "DOI": "10.1016/j.ijid.2020.08.076", "article-title": "Asymptomatic SARS coronavirus 2 infection: invisible yet invincible", "author": "Nikolai", "doi-asserted-by": "crossref", "first-page": "112", "journal-title": "Int J Infect Dis", "key": "2026031805360758600_vkag017-B13", "volume": "100", "year": "2020" }, { "DOI": "10.1038/mi.2014.11", "article-title": "The development and function of mucosal lymphoid tissues: a balancing act with micro-organisms", "author": "Randall", "doi-asserted-by": "crossref", "first-page": "455", "journal-title": "Mucosal Immunol", "key": "2026031805360758600_vkag017-B14", "volume": "7", "year": "2014" }, { "DOI": "10.1016/j.tim.2020.12.007", "article-title": "Dysregulation of cell signaling by SARS-CoV-2", "author": "Suryawanshi", "doi-asserted-by": "crossref", "first-page": "224", "journal-title": "Trends Microbiol", "key": "2026031805360758600_vkag017-B15", "volume": "29", "year": "2021" }, { "DOI": "10.3390/vaccines10081173", "article-title": "Considerations for novel COVID-19 mucosal vaccine development", "author": "Alturaiki", "doi-asserted-by": "crossref", "first-page": "1173", "journal-title": "Vaccines (Basel)", "key": "2026031805360758600_vkag017-B16", "volume": "10", "year": "2022" }, { "DOI": "10.1038/nm0606-614", "article-title": "T cells take the inside track", "author": "Openshaw", "doi-asserted-by": "crossref", "first-page": "614", "journal-title": "Nat Med", "key": "2026031805360758600_vkag017-B17", "volume": "12", "year": "2006" }, { "DOI": "10.1097/TA.0000000000004184", "article-title": "Dimethyl malonate protects the lung in a murine model of acute respiratory distress syndrome", "author": "Taghavi", "doi-asserted-by": "crossref", "first-page": "386", "journal-title": "J Trauma Acute Care Surg", "key": "2026031805360758600_vkag017-B18", "volume": "96", "year": "2024" }, { "DOI": "10.1016/j.intimp.2018.11.019", "article-title": "Preclinical development of the TLR9 agonist DV281 as an inhaled aerosolized immunotherapeutic for lung cancer: pharmacological profile in mice, non-human primates, and human primary cells", "author": "Kell", "doi-asserted-by": "crossref", "first-page": "296", "journal-title": "Int Immunopharmacol", "key": "2026031805360758600_vkag017-B19", "volume": "66", "year": "2019" }, { "DOI": "10.1073/pnas.1110144108", "article-title": "Neutrophil transmigration triggers repair of the lung epithelium via beta-catenin signaling", "author": "Zemans", "doi-asserted-by": "crossref", "first-page": "15990", "journal-title": "Proc Natl Acad Sci U S A", "key": "2026031805360758600_vkag017-B20", "volume": "108", "year": "2011" }, { "DOI": "10.1158/1940-6207.CAPR-11-0212", "article-title": "Characterizing the impact of smoking and lung cancer on the airway transcriptome using RNA-Seq", "author": "Beane", "doi-asserted-by": "crossref", "first-page": "803", "journal-title": "Cancer Prev Res (Phila)", "key": "2026031805360758600_vkag017-B21", "volume": "4", "year": "2011" }, { "DOI": "10.1016/j.imbio.2008.01.005", "article-title": "CXCR6 identifies a putative population of retained human lung T cells characterised by co-expression of activation markers", "author": "Morgan", "doi-asserted-by": "crossref", "first-page": "599", "journal-title": "Immunobiology", "key": "2026031805360758600_vkag017-B22", "volume": "213", "year": "2008" }, { "DOI": "10.1046/j.1365-2745.2002.01444.x", "article-title": "Cetirizine and levocetirizine inhibit eotaxin-induced eosinophil transendothelial migration through human dermal or lung microvascular endothelial cells", "author": "Thomson", "doi-asserted-by": "crossref", "first-page": "1187", "journal-title": "Clin Exp Allergy", "key": "2026031805360758600_vkag017-B23", "volume": "32", "year": "2002" }, { "DOI": "10.4049/jimmunol.166.4.2842", "article-title": "Expression of chemokine receptors by lung T cells from normal and asthmatic subjects", "author": "Campbell", "doi-asserted-by": "crossref", "first-page": "2842", "journal-title": "J Immunol", "key": "2026031805360758600_vkag017-B24", "volume": "166", "year": "2001" }, { "DOI": "10.1136/gut.47.6.838", "article-title": "Treatment with neutralising antibody against cytokine induced neutrophil chemoattractant (CINC) protects rats against acute pancreatitis associated lung injury", "author": "Bhatia", "doi-asserted-by": "crossref", "first-page": "838", "journal-title": "Gut", "key": "2026031805360758600_vkag017-B25", "volume": "47", "year": "2000" }, { "DOI": "10.3390/ijms232415638", "article-title": "CC Chemokine receptor 4 (CCR4) as a possible new target for therapy", "author": "Bogacka", "doi-asserted-by": "crossref", "first-page": "15638", "journal-title": "Int J Mol Sci", "key": "2026031805360758600_vkag017-B26", "volume": "23", "year": "2022" }, { "DOI": "10.1111/all.16036", "article-title": "CXCL17 induces activation of human mast cells via MRGPRX2", "author": "Ding", "doi-asserted-by": "crossref", "first-page": "1609", "journal-title": "Allergy", "key": "2026031805360758600_vkag017-B27", "volume": "79", "year": "2024" }, { "DOI": "10.1002/jbt.20240", "article-title": "Endosulfan-induced apoptosis and glutathione depletion in human peripheral blood mononuclear cells: attenuation by N-acetylcysteine", "author": "Ahmed", "doi-asserted-by": "crossref", "first-page": "299", "journal-title": "J Biochem Mol Toxicol", "key": "2026031805360758600_vkag017-B28", "volume": "22", "year": "2008" }, { "DOI": "10.4049/jimmunol.1700884", "article-title": "Evidence for the existence of a CXCL17 receptor distinct from GPR35", "author": "Binti Mohd Amir", "doi-asserted-by": "crossref", "first-page": "714", "journal-title": "J Immunol", "key": "2026031805360758600_vkag017-B29", "volume": "201", "year": "2018" }, { "DOI": "10.4049/jimmunol.176.4.2069", "article-title": "Cutting edge: novel human dendritic cell- and monocyte-attracting chemokine-like protein identified by fold recognition methods", "author": "Pisabarro", "doi-asserted-by": "crossref", "first-page": "2069", "journal-title": "J Immunol", "key": "2026031805360758600_vkag017-B30", "volume": "176", "year": "2006" }, { "DOI": "10.1016/j.bbrc.2006.08.194", "article-title": "VCC-1, a novel chemokine, promotes tumor growth", "author": "Weinstein", "doi-asserted-by": "crossref", "first-page": "74", "journal-title": "Biochem Biophys Res Commun", "key": "2026031805360758600_vkag017-B31", "volume": "350", "year": "2006" }, { "DOI": "10.1016/j.cytogfr.2020.04.004", "article-title": "The protective and pathogenic roles of CXCL17 in human health and disease: potential in respiratory medicine", "author": "Choreno-Parra", "doi-asserted-by": "crossref", "first-page": "53", "journal-title": "Cytokine Growth Factor Rev", "key": "2026031805360758600_vkag017-B32", "volume": "53", "year": "2020" }, { "DOI": "10.1007/s10067-019-04775-z", "article-title": "Increased circulating CXCL13 levels in systemic lupus erythematosus and rheumatoid arthritis: a meta-analysis", "author": "Bao", "doi-asserted-by": "crossref", "first-page": "281", "journal-title": "Clin Rheumatol", "key": "2026031805360758600_vkag017-B33", "volume": "39", "year": "2020" }, { "DOI": "10.1186/s13018-024-04645-8", "article-title": "Correlation of serum and local CXCL13 levels with disease severity in patients with non-traumatic osteonecrosis of femoral head", "author": "Zhao", "doi-asserted-by": "crossref", "first-page": "162", "journal-title": "J Orthop Surg Res", "key": "2026031805360758600_vkag017-B34", "volume": "19", "year": "2024" }, { "DOI": "10.1016/j.it.2023.10.003", "article-title": "Homeostatic chemokines as putative therapeutic targets in idiopathic pulmonary fibrosis", "author": "Russo", "doi-asserted-by": "crossref", "first-page": "1014", "journal-title": "Trends Immunol", "key": "2026031805360758600_vkag017-B35", "volume": "44", "year": "2023" }, { "article-title": "Anti-inflammatory drug development: broad or specific chemokine receptor antagonists?", "author": "Russo", "first-page": "414", "journal-title": "Curr Opin Drug Discov Devel", "key": "2026031805360758600_vkag017-B36", "volume": "13", "year": "2010" }, { "DOI": "10.1124/pr.113.007724", "article-title": "International union of basic and clinical pharmacology. [corrected]. LXXXIX. Update on the extended family of chemokine receptors and introducing a new nomenclature for atypical chemokine receptors", "author": "Bachelerie", "doi-asserted-by": "crossref", "first-page": "1", "journal-title": "Pharmacol Rev", "key": "2026031805360758600_vkag017-B37", "volume": "66", "year": "2014" }, { "DOI": "10.3390/ijms24076322", "article-title": "IL-10 promotes CXCL13 expression in macrophages following foot-and-mouth disease virus infection", "author": "Guo", "doi-asserted-by": "crossref", "first-page": "6322", "journal-title": "Int J Mol Sci", "key": "2026031805360758600_vkag017-B38", "volume": "24", "year": "2023" }, { "DOI": "10.4049/jimmunol.1900790", "article-title": "TNF-alpha and IL-10 control CXCL13 expression in human macrophages", "author": "Bellamri", "doi-asserted-by": "crossref", "first-page": "2492", "journal-title": "J Immunol", "key": "2026031805360758600_vkag017-B39", "volume": "204", "year": "2020" }, { "DOI": "10.3390/v14122665", "article-title": "CXCL12 and CXCL13 cytokine serum levels are associated with the magnitude and the quality of SARS-CoV-2 humoral responses", "author": "Noto", "doi-asserted-by": "crossref", "first-page": "2665", "journal-title": "Viruses", "key": "2026031805360758600_vkag017-B40", "volume": "14", "year": "2022" }, { "DOI": "10.1093/infdis/jiad590", "article-title": "Delayed mucosal antiviral responses despite robust peripheral inflammation in fatal COVID-19", "author": "Sidhu", "doi-asserted-by": "crossref", "first-page": "e17", "journal-title": "J Infect Dis", "key": "2026031805360758600_vkag017-B41", "volume": "230", "year": "2024" }, { "DOI": "10.1038/s41467-021-25191-5", "article-title": "The cytokines HGF and CXCL13 predict the severity and the mortality in COVID-19 patients", "author": "Perreau", "doi-asserted-by": "crossref", "first-page": "4888", "journal-title": "Nat Commun", "key": "2026031805360758600_vkag017-B42", "volume": "12", "year": "2021" }, { "DOI": "10.1016/j.virol.2020.05.015", "article-title": "Growth, detection, quantification, and inactivation of SARS-CoV-2", "author": "Case", "doi-asserted-by": "crossref", "first-page": "39", "journal-title": "Virology", "key": "2026031805360758600_vkag017-B43", "volume": "548", "year": "2020" }, { "first-page": "1343716", "key": "2026031805360758600_vkag017-B44", "year": "2024" }, { "DOI": "10.1101/2022.07.22.501208", "author": "Dhanushkodi", "doi-asserted-by": "publisher", "key": "2026031805360758600_vkag017-B45", "year": "2022" }, { "DOI": "10.1101/2022.07.22.501208", "article-title": "Prime/Pull RR2/CXCL11 therapeutic vaccine that bolsters the number and function of dorsal root ganglia tissue-resident HSV-specific CD8 TRM cells protects latently infected guinea pigs from recurrent genital herpes", "author": "Dhanushkodi", "doi-asserted-by": "publisher", "first-page": "501", "journal-title": "bioRxiv", "key": "2026031805360758600_vkag017-B46", "volume": "2022", "year": "2022" }, { "DOI": "10.1084/jem.187.4.655", "article-title": "B cell-attracting chemokine 1, a human CXC chemokine expressed in lymphoid tissues, selectively attracts B lymphocytes via BLR1/CXCR5", "author": "Legler", "doi-asserted-by": "crossref", "first-page": "655", "journal-title": "J Exp Med", "key": "2026031805360758600_vkag017-B47", "volume": "187", "year": "1998" }, { "DOI": "10.1038/35876", "article-title": "A B-cell-homing chemokine made in lymphoid follicles activates Burkitt’s lymphoma receptor-1", "author": "Gunn", "doi-asserted-by": "crossref", "first-page": "799", "journal-title": "Nature", "key": "2026031805360758600_vkag017-B48", "volume": "391", "year": "1998" }, { "article-title": "Chemokines and B-cell homing to follicles", "author": "Cyster", "first-page": "87", "journal-title": "Curr Top Microbiol Immunol", "key": "2026031805360758600_vkag017-B49", "volume": "246", "year": "1999" }, { "DOI": "10.1128/mSphere.01324-20", "article-title": "Interplay of antibody and cytokine production reveals CXCL13 as a potential novel biomarker of lethal SARS-CoV-2 infection", "author": "Horspool", "doi-asserted-by": "crossref", "first-page": "e01324", "journal-title": "mSphere", "key": "2026031805360758600_vkag017-B50", "volume": "6", "year": "2021" }, { "DOI": "10.1084/jem.20181216", "article-title": "Type I interferon induces CXCL13 to support ectopic germinal center formation", "author": "Denton", "doi-asserted-by": "crossref", "first-page": "621", "journal-title": "J Exp Med", "key": "2026031805360758600_vkag017-B51", "volume": "216", "year": "2019" }, { "DOI": "10.1016/j.cell.2021.01.007", "article-title": "Adaptive immunity to SARS-CoV-2 and COVID-19", "author": "Sette", "doi-asserted-by": "crossref", "first-page": "861", "journal-title": "Cell", "key": "2026031805360758600_vkag017-B52", "volume": "184", "year": "2021" }, { "DOI": "10.1007/s00705-023-05773-y", "article-title": "B lymphocytes in COVID-19: a tale of harmony and discordance", "author": "Mansourabadi", "doi-asserted-by": "crossref", "first-page": "148", "journal-title": "Arch Virol", "key": "2026031805360758600_vkag017-B53", "volume": "168", "year": "2023" }, { "DOI": "10.1126/sciadv.adg2122", "article-title": "Repetitive mRNA vaccination is required to improve the quality of broad-spectrum anti-SARS-CoV-2 antibodies in the absence of CXCL13", "author": "Azarias Da Silva", "doi-asserted-by": "crossref", "first-page": "eadg2122", "journal-title": "Sci Adv", "key": "2026031805360758600_vkag017-B54", "volume": "9", "year": "2023" }, { "DOI": "10.1164/rccm.201211-2055OC", "article-title": "Role of CXCL13 in cigarette smoke-induced lymphoid follicle formation and chronic obstructive pulmonary disease", "author": "Bracke", "doi-asserted-by": "crossref", "first-page": "343", "journal-title": "Am J Respir Crit Care Med", "key": "2026031805360758600_vkag017-B55", "volume": "188", "year": "2013" }, { "DOI": "10.1164/rccm.201309-1592OC", "article-title": "C-X-C motif chemokine 13 (CXCL13) is a prognostic biomarker of idiopathic pulmonary fibrosis", "author": "Vuga", "doi-asserted-by": "crossref", "first-page": "966", "journal-title": "Am J Respir Crit Care Med", "key": "2026031805360758600_vkag017-B56", "volume": "189", "year": "2014" }, { "DOI": "10.1159/000503689", "article-title": "Evaluation of the diagnostic efficacies of serological markers KL-6, SP-A, SP-D, CCL2, and CXCL13 in idiopathic interstitial pneumonia", "author": "Xue", "doi-asserted-by": "crossref", "first-page": "534", "journal-title": "Respiration", "key": "2026031805360758600_vkag017-B57", "volume": "98", "year": "2019" }, { "article-title": "Elevated plasma levels of CXCL13 chemokine in Saudi patients with asthma exacerbation", "author": "Alturaiki", "first-page": "e21142", "journal-title": "Cureus", "key": "2026031805360758600_vkag017-B58", "volume": "14", "year": "2022" }, { "DOI": "10.12688/f1000research.14556.2", "article-title": "Role of CXCL13 in the formation of the meningeal tertiary lymphoid organ in multiple sclerosis", "author": "Londono", "doi-asserted-by": "crossref", "first-page": "514", "journal-title": "F1000Res", "key": "2026031805360758600_vkag017-B59", "volume": "7", "year": "2018" }, { "DOI": "10.1164/rccm.201208-1543OC", "article-title": "CXCL13 production in B cells via Toll-like receptor/lymphotoxin receptor signaling is involved in lymphoid neogenesis in chronic obstructive pulmonary disease", "author": "Litsiou", "doi-asserted-by": "crossref", "first-page": "1194", "journal-title": "Am J Respir Crit Care Med", "key": "2026031805360758600_vkag017-B60", "volume": "187", "year": "2013" }, { "DOI": "10.1182/blood.2024027884", "article-title": "Decoding functional hematopoietic progenitor cells in the adult human lung", "author": "Conrad", "doi-asserted-by": "crossref", "first-page": "1975", "journal-title": "Blood", "key": "2026031805360758600_vkag017-B61", "volume": "145", "year": "2025" }, { "DOI": "10.1016/j.mucimm.2025.05.005", "article-title": "Inflammatory chemokine receptors CCR1, CCR2, CCR3 and CCR5 are essential for an optimal T cell response to influenza", "author": "Pingen", "doi-asserted-by": "crossref", "first-page": "951", "journal-title": "Mucosal Immunol", "key": "2026031805360758600_vkag017-B62", "volume": "18", "year": "2025" }, { "DOI": "10.1172/jci.insight.157215", "article-title": "CXCL13-producing CD4+ T cells accumulate in the early phase of tertiary lymphoid structures in ovarian cancer", "author": "Ukita", "doi-asserted-by": "crossref", "journal-title": "JCI Insight", "key": "2026031805360758600_vkag017-B63", "volume": "7", "year": "2022" }, { "DOI": "10.3389/fimmu.2022.997862", "article-title": "CXCL13 is elevated in inflammatory bowel disease in mice and humans and is implicated in disease pathogenesis", "author": "Liu", "doi-asserted-by": "crossref", "first-page": "997862", "journal-title": "Front Immunol", "key": "2026031805360758600_vkag017-B64", "volume": "13", "year": "2022" }, { "DOI": "10.4049/jimmunol.176.12.7676", "article-title": "CXC chemokine ligand 13 plays a role in experimental autoimmune encephalomyelitis", "author": "Bagaeva", "doi-asserted-by": "crossref", "first-page": "7676", "journal-title": "J Immunol", "key": "2026031805360758600_vkag017-B65", "volume": "176", "year": "2006" }, { "DOI": "10.3389/fimmu.2024.1382638", "article-title": "B cells in the pneumococcus-infected lung are heterogeneous and require CD4(+) T cell help including CD40L to become resident memory B cells", "author": "Etesami", "doi-asserted-by": "crossref", "first-page": "1382638", "journal-title": "Front Immunol", "key": "2026031805360758600_vkag017-B66", "volume": "15", "year": "2024" }, { "DOI": "10.1073/pnas.2406434121", "article-title": "CXCL13 promotes broad immune responses induced by circular RNA vaccines", "author": "Wan", "doi-asserted-by": "crossref", "first-page": "e2406434121", "journal-title": "Proc Natl Acad Sci U S A", "key": "2026031805360758600_vkag017-B67", "volume": "121", "year": "2024" }, { "DOI": "10.1016/j.bbcan.2022.188799", "article-title": "CXCL13-CXCR5 axis: regulation in inflammatory diseases and cancer", "author": "Wang", "doi-asserted-by": "crossref", "first-page": "188799", "journal-title": "Biochim Biophys Acta Rev Cancer", "key": "2026031805360758600_vkag017-B68", "volume": "1877", "year": "2022" }, { "DOI": "10.1016/S1074-7613(01)00257-6", "article-title": "CXCL13 is required for B1 cell homing, natural antibody production, and body cavity immunity", "author": "Ansel", "doi-asserted-by": "crossref", "first-page": "67", "journal-title": "Immunity", "key": "2026031805360758600_vkag017-B69", "volume": "16", "year": "2002" }, { "DOI": "10.1016/j.bbi.2016.01.016", "article-title": "CXCL13 promotes isotype-switched B cell accumulation to the central nervous system during viral encephalomyelitis", "author": "Phares", "doi-asserted-by": "crossref", "first-page": "128", "journal-title": "Brain Behav Immun", "key": "2026031805360758600_vkag017-B70", "volume": "54", "year": "2016" }, { "DOI": "10.1097/TXD.0000000000001247", "article-title": "CXCL13 is an indicator of germinal center activity and alloantibody formation following transplantation", "author": "Crichton", "doi-asserted-by": "crossref", "first-page": "e785", "journal-title": "Transplant Direct", "key": "2026031805360758600_vkag017-B71", "volume": "7", "year": "2021" }, { "DOI": "10.1128/JVI.76.6.2780-2788.2002", "article-title": "Herpes simplex virus selectively induces expression of the CC chemokine RANTES/CCL5 in macrophages through a mechanism dependent on PKR and ICP0", "author": "Melchjorsen", "doi-asserted-by": "crossref", "first-page": "2780", "journal-title": "J Virol", "key": "2026031805360758600_vkag017-B72", "volume": "76", "year": "2002" }, { "DOI": "10.4049/jimmunol.2100341", "article-title": "CXCL13 as a novel immune checkpoint for regulatory B cells and its role in tumor metastasis", "author": "Ren", "doi-asserted-by": "crossref", "first-page": "2425", "journal-title": "J Immunol", "key": "2026031805360758600_vkag017-B73", "volume": "208", "year": "2022" }, { "DOI": "10.1016/j.lfs.2021.119251", "article-title": "Targeting RAGE to prevent SARS-CoV-2-mediated multiple organ failure: hypotheses and perspectives", "author": "Chiappalupi", "doi-asserted-by": "crossref", "first-page": "119251", "journal-title": "Life Sci", "key": "2026031805360758600_vkag017-B74", "volume": "272", "year": "2021" }, { "DOI": "10.1007/s40139-021-00226-0", "article-title": "Chemokine-based therapeutics for the treatment of inflammatory and fibrotic convergent pathways in COVID-19", "author": "Julian", "doi-asserted-by": "crossref", "first-page": "93", "journal-title": "Curr Pathobiol Rep", "key": "2026031805360758600_vkag017-B75", "volume": "9", "year": "2021" }, { "DOI": "10.3389/fmicb.2021.698169", "article-title": "Long COVID or Post-acute sequelae of COVID-19 (PASC): an overview of biological factors that may contribute to persistent symptoms", "author": "Proal", "doi-asserted-by": "crossref", "first-page": "698169", "journal-title": "Front Microbiol", "key": "2026031805360758600_vkag017-B76", "volume": "12", "year": "2021" }, { "DOI": "10.1126/scitranslmed.ado2104", "article-title": "Animal models of long Covid: a hit-and-run disease", "author": "Schafer", "doi-asserted-by": "crossref", "first-page": "eado2104", "journal-title": "Sci Transl Med", "key": "2026031805360758600_vkag017-B77", "volume": "16", "year": "2024" }, { "DOI": "10.3390/pathogens14040346", "article-title": "Weathering the storm: how age and biologics influence the COVID-19 cytokine surge", "author": "Astroth", "doi-asserted-by": "crossref", "first-page": "346", "journal-title": "Pathogens", "key": "2026031805360758600_vkag017-B78", "volume": "14", "year": "2025" }, { "DOI": "10.1371/journal.pone.0293883", "article-title": "Predictors of early and long-term mortality after ICU discharge in critically ill COVID-19 patients: a prospective cohort study", "author": "Santos", "doi-asserted-by": "crossref", "first-page": "e0293883", "journal-title": "PloS One", "key": "2026031805360758600_vkag017-B79", "volume": "18", "year": "2023" }, { "DOI": "10.3389/fimmu.2023.1111797", "article-title": "Different cytokine and chemokine profiles in hospitalized patients with COVID-19 during the first and second outbreaks from Argentina show no association with clinical comorbidities", "author": "Almada", "doi-asserted-by": "crossref", "first-page": "1111797", "journal-title": "Front Immunol", "key": "2026031805360758600_vkag017-B80", "volume": "14", "year": "2023" }, { "DOI": "10.1136/jitc-2020-001136", "article-title": "CXCL13 shapes immunoactive tumor microenvironment and enhances the efficacy of PD-1 checkpoint blockade in high-grade serous ovarian cancer", "author": "Yang", "doi-asserted-by": "crossref", "journal-title": "J Immunother Cancer", "key": "2026031805360758600_vkag017-B81", "volume": "9", "year": "2021" }, { "DOI": "10.1126/scitranslmed.abc4220", "article-title": "ARID1A mutation plus CXCL13 expression act as combinatorial biomarkers to predict responses to immune checkpoint therapy in mUCC", "author": "Goswami", "doi-asserted-by": "crossref", "journal-title": "Sci Transl Med", "key": "2026031805360758600_vkag017-B82", "volume": "12", "year": "2020" }, { "DOI": "10.3390/cancers14020294", "article-title": "Potential role of CXCL13/CXCR5 signaling in immune checkpoint inhibitor treatment in cancer", "author": "Hsieh", "doi-asserted-by": "crossref", "first-page": "294", "journal-title": "Cancers (Basel)", "key": "2026031805360758600_vkag017-B83", "volume": "14", "year": "2022" }, { "DOI": "10.1038/s43018-022-00433-7", "article-title": "Single-cell meta-analyses reveal responses of tumor-reactive CXCL13(+) T cells to immune-checkpoint blockade", "author": "Liu", "doi-asserted-by": "crossref", "first-page": "1123", "journal-title": "Nat Cancer", "key": "2026031805360758600_vkag017-B84", "volume": "3", "year": "2022" }, { "DOI": "10.1002/cam4.5460", "article-title": "Transcriptional upregulation of CXCL13 is correlated with a favorable response to immune checkpoint inhibitors in lung adenocarcinoma", "author": "Park", "doi-asserted-by": "crossref", "first-page": "7639", "journal-title": "Cancer Med", "key": "2026031805360758600_vkag017-B85", "volume": "12", "year": "2023" }, { "DOI": "10.1007/s12033-024-01207-5", "article-title": "Identification of CXCL13 as a promising biomarker for immune checkpoint blockade therapy and PARP inhibitor therapy in ovarian cancer", "author": "Ding", "doi-asserted-by": "crossref", "first-page": "2428", "journal-title": "Mol Biotechnol", "key": "2026031805360758600_vkag017-B86", "volume": "67", "year": "2025" }, { "DOI": "10.1111/ene.16279", "article-title": "Beyond T cell toxicity—Intrathecal chemokine CXCL13 indicating B cell involvement in immune-related adverse events following checkpoint inhibition: a two-case series and literature review", "author": "Otto", "doi-asserted-by": "crossref", "first-page": "e16279", "journal-title": "Eur J Neurol", "key": "2026031805360758600_vkag017-B87", "volume": "31", "year": "2024" }, { "DOI": "10.1177/09612033251319405", "article-title": "Serum CXCL-13 levels are associated with active neurological involvement in patients with systemic lupus erythematosus", "author": "Yildirim", "doi-asserted-by": "crossref", "first-page": "281", "journal-title": "Lupus", "key": "2026031805360758600_vkag017-B88", "volume": "34", "year": "2025" }, { "article-title": "Mesenteric lymphatic B cells migrate to the intestine and aggravate DSS-induced colitis via the CXCR5-CXCL13 axis", "author": "Zhang", "first-page": "322", "journal-title": "Biology (Basel)", "key": "2026031805360758600_vkag017-B89", "volume": "13", "year": "2024" }, { "DOI": "10.1038/s41590-023-01724-6", "article-title": "Long COVID manifests with T cell dysregulation, inflammation and an uncoordinated adaptive immune response to SARS-CoV-2", "author": "Yin", "doi-asserted-by": "crossref", "first-page": "218", "journal-title": "Nat Immunol", "key": "2026031805360758600_vkag017-B90", "volume": "25", "year": "2024" }, { "DOI": "10.1016/j.thromres.2024.109196", "article-title": "CXCL13/CXCR5 axis facilitates TFH expansion and correlates with disease severity in adults with immune thrombocytopenia", "author": "Chen", "doi-asserted-by": "crossref", "first-page": "109196", "journal-title": "Thromb Res", "key": "2026031805360758600_vkag017-B91", "volume": "244", "year": "2024" } ], "reference-count": 91, "references-count": 91, "relation": {}, "resource": { "primary": { "URL": "https://academic.oup.com/jimmunol/article/doi/10.1093/jimmun/vkag017/8527216" } }, "score": 1, "short-title": [], "source": "Crossref", "subject": [], "subtitle": [], "title": "CXCL13/CXCR5 chemokine axis promotes antiviral CXCR5+CD19+ B Cells and follicular/effector CXCR5+CD4+ T Cells in the lungs associated with protection from severe and fatal COVID-19 following infection with pathogenic SARS-CoV-2 Delta variant", "type": "journal-article", "volume": "215" }