{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T19:55:56Z","timestamp":1775073356121,"version":"3.50.1"},"reference-count":50,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2023,7,21]],"date-time":"2023-07-21T00:00:00Z","timestamp":1689897600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,9,27]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Targeting CXCR1 and CXCR2 chemokine receptors to block neutrophil migration to sites of inflammation is a promising therapeutic approach for various inflammatory and autoimmune diseases. However, assessing the translational potential of such therapies using mouse models is challenging due to the unclear expression of CXCR1 at the protein level. Although CXCR2 has been well characterized in both mice and humans, the protein-level expression of CXCR1 in mice (mCXCR1) remains controversial. To address this issue, we generated a novel human CXCR1 knock-in (hCXCR1 KI) mouse model in which the transgene is under the control of the native mouse promoter and regulatory elements. Using an anti-human CXCR1 monoclonal antibody (anti-hCXCR1 monoclonal antibody), we found that hCXCR1 was highly expressed on neutrophils in the hCXCR1 KI mice, comparable to levels observed in human neutrophils. This successful expression of hCXCR1 in this mouse model suggests that functional mCXCR1 likely exists. To investigate the functional role of CXCR1, we investigated how antagonizing this receptor using anti-hCXCR1 monoclonal antibody in the arthritis model would affect disease outcomes. Antibody treatment significantly alleviated all signs of joint inflammation. In summary, our newly generated hCXCR1 KI transgenic mice provide a valuable tool to investigate the therapeutic efficacy of small molecules or monoclonal antibodies that antagonize this receptor in neutrophil-mediated pathologies.<\/jats:p>","DOI":"10.1093\/jleuko\/qiad085","type":"journal-article","created":{"date-parts":[[2023,7,21]],"date-time":"2023-07-21T19:36:46Z","timestamp":1689968206000},"page":"373-380","source":"Crossref","is-referenced-by-count":3,"title":["Human CXCR1 knock-in mice infer functional expression of a murine ortholog"],"prefix":"10.1093","volume":"114","author":[{"given":"Farnaz","family":"Fahimi","sequence":"first","affiliation":[{"name":"Department of Physiology, Biomedicine Discovery Institute, Monash University , Clayton, Victoria 3800 , Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7935-6346","authenticated-orcid":false,"given":"Md Jahangir","family":"Alam","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Biomedicine Discovery Institute, Monash University , Clayton, Victoria 3800 , Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Caroline","family":"Ang","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University , Clayton, Victoria 3800 , Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Galih Prakasa","family":"Adhyatma","sequence":"additional","affiliation":[{"name":"Department of Physiology, Biomedicine Discovery Institute, Monash University , Clayton, Victoria 3800 , Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liang","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Biomedicine Discovery Institute, Monash University , Clayton, Victoria 3800 , Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6338-7340","authenticated-orcid":false,"given":"Charles R","family":"Mackay","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Biomedicine Discovery Institute, Monash University , Clayton, Victoria 3800 , Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2416-9268","authenticated-orcid":false,"given":"Remy","family":"Robert","sequence":"additional","affiliation":[{"name":"Department of Physiology, Biomedicine Discovery Institute, Monash University , Clayton, Victoria 3800 , Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2023,7,21]]},"reference":[{"issue":"1","key":"2023101106481785100_qiad085-B1","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1146\/annurev-pathol-020712-164023","article-title":"The multifaceted functions of neutrophils","volume":"9","author":"Mayadas","year":"2014","journal-title":"Annu Rev Pathol"},{"issue":"1","key":"2023101106481785100_qiad085-B2","doi-asserted-by":"crossref","first-page":"1856460","DOI":"10.1080\/19420862.2020.1856460","article-title":"Therapeutic blockade of CXCR2 rapidly clears inflammation in arthritis and atopic dermatitis models: demonstration with surrogate and humanized antibodies","volume":"12","author":"Alam","year":"2020","journal-title":"MAbs"},{"issue":"1","key":"2023101106481785100_qiad085-B3","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1124\/jpet.108.145862","article-title":"Therapeutic effect of blocking CXCR2 on neutrophil recruitment and dextran sodium sulfate-induced colitis","volume":"329","author":"Farooq","year":"2009","journal-title":"J Pharmacol Exp Ther"},{"issue":"1","key":"2023101106481785100_qiad085-B4","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.yexmp.2003.08.004","article-title":"Contrasting roles for CXCR2 during experimental colitis","volume":"76","author":"Ajuebor","year":"2004","journal-title":"Exp Mol Pathol"},{"issue":"1","key":"2023101106481785100_qiad085-B5","doi-asserted-by":"crossref","first-page":"5166","DOI":"10.1038\/s41467-019-13107-3","article-title":"Chemokine receptor trafficking coordinates neutrophil clustering and dispersal at wounds in zebrafish","volume":"10","author":"Coombs","year":"2019","journal-title":"Nat Commun"},{"issue":"6","key":"2023101106481785100_qiad085-B6","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1038\/nri.2016.49","article-title":"Neutrophil migration in infection and wound repair: going forward in reverse","volume":"16","author":"de Oliveira","year":"2016","journal-title":"Nat Rev Immunol"},{"issue":"7426","key":"2023101106481785100_qiad085-B7","doi-asserted-by":"crossref","first-page":"779","DOI":"10.1038\/nature11580","article-title":"Structure of the chemokine receptor CXCR1 in phospholipid bilayers","volume":"491","author":"Park","year":"2012","journal-title":"Nature"},{"issue":"5","key":"2023101106481785100_qiad085-B8","doi-asserted-by":"crossref","first-page":"3425","DOI":"10.4049\/jimmunol.0900305","article-title":"Differential activation and regulation of CXCR1 and CXCR2 by CXCL8 monomer and dimer","volume":"183","author":"Nasser","year":"2009","journal-title":"J Immunol"},{"issue":"5025","key":"2023101106481785100_qiad085-B9","doi-asserted-by":"crossref","first-page":"1280","DOI":"10.1126\/science.1891716","article-title":"Cloning of complementary DNA encoding a functional human interleukin-8 receptor","volume":"253","author":"Murphy","year":"1991","journal-title":"Science"},{"issue":"1","key":"2023101106481785100_qiad085-B10","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1038\/ng0992-31","article-title":"Molecular evolution of the human interleukin-8 receptor gene cluster","volume":"2","author":"Ahuja","year":"1992","journal-title":"Nat Genet"},{"issue":"9","key":"2023101106481785100_qiad085-B11","doi-asserted-by":"crossref","first-page":"781","DOI":"10.1007\/s10038-006-0021-5","article-title":"Polymorphisms in interleukin 8 and its receptors (IL8, IL8RA and IL8RB) and association of common IL8 receptor variants with peripheral blood eosinophil counts","volume":"51","author":"Cheong","year":"2006","journal-title":"J Hum Genet"},{"issue":"2","key":"2023101106481785100_qiad085-B12","first-page":"95","article-title":"Chemokines and chemokine receptors: their manifold roles in homeostasis and disease","volume":"1","author":"Le","year":"2004","journal-title":"Cell Mol Immunol"},{"issue":"6","key":"2023101106481785100_qiad085-B13","doi-asserted-by":"crossref","first-page":"2904","DOI":"10.4049\/jimmunol.170.6.2904","article-title":"Role of the cytoplasmic tails of CXCR1 and CXCR2 in mediating leukocyte migration, activation, and regulation","volume":"170","author":"Richardson","year":"2003","journal-title":"J Immunol"},{"issue":"6","key":"2023101106481785100_qiad085-B14","doi-asserted-by":"crossref","first-page":"2824","DOI":"10.4049\/jimmunol.1201114","article-title":"The chemokine receptors CXCR1 and CXCR2 couple to distinct G protein-coupled receptor kinases to mediate and regulate leukocyte functions","volume":"189","author":"Raghuwanshi","year":"2012","journal-title":"J Immunol"},{"key":"2023101106481785100_qiad085-B15","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.cytogfr.2016.08.002","article-title":"The CXCL8-CXCR1\/2 pathways in cancer","volume":"31","author":"Liu","year":"2016","journal-title":"Cytokine Growth Factor Rev"},{"key":"2023101106481785100_qiad085-B16","doi-asserted-by":"crossref","first-page":"111853","DOI":"10.1016\/j.ejmech.2019.111853","article-title":"Targeting CXCR1\/2: the medicinal potential as cancer immunotherapy agents, antagonists research highlights and challenges ahead","volume":"185","author":"Che","year":"2020","journal-title":"Eur J Med Chem"},{"issue":"5","key":"2023101106481785100_qiad085-B17","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1177\/1535370213520110","article-title":"Blockade of CXCR2 signalling: a potential therapeutic target for preventing neutrophil-mediated inflammatory diseases","volume":"239","author":"Boppana","year":"2014","journal-title":"Exp Biol Med (Maywood)"},{"issue":"9","key":"2023101106481785100_qiad085-B18","doi-asserted-by":"crossref","first-page":"5287","DOI":"10.4049\/jimmunol.165.9.5287","article-title":"Transepithelial neutrophil migration is CXCR1 dependent in vitro and is defective in IL-8 receptor knockout mice","volume":"165","author":"Godaly","year":"2000","journal-title":"J Immunol"},{"issue":"1","key":"2023101106481785100_qiad085-B19","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.cyto.2005.02.005","article-title":"Cloning and characterization of mouse homolog of the CXC chemokine receptor CXCR1","volume":"31","author":"Fu","year":"2005","journal-title":"Cytokine"},{"issue":"7","key":"2023101106481785100_qiad085-B20","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1016\/j.molimm.2005.06.043","article-title":"A homolog of the human chemokine receptor CXCR1 is expressed in the mouse","volume":"43","author":"Moepps","year":"2006","journal-title":"Mol Immunol"},{"issue":"16","key":"2023101106481785100_qiad085-B21","doi-asserted-by":"crossref","first-page":"11658","DOI":"10.1074\/jbc.M607705200","article-title":"Murine CXCR1 is a functional receptor for GCP-2\/CXCL6 and interleukin-8\/CXCL8","volume":"282","author":"Fan","year":"2007","journal-title":"J Biol Chem"},{"issue":"2","key":"2023101106481785100_qiad085-B22","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1016\/j.bbcan.2019.01.005","article-title":"Potential roles and targeted therapy of the CXCLs\/CXCR2 axis in cancer and inflammatory diseases","volume":"1871","author":"Cheng","year":"2019","journal-title":"Biochim Biophys Acta Rev Cancer"},{"issue":"7","key":"2023101106481785100_qiad085-B23","doi-asserted-by":"crossref","first-page":"e0134365","DOI":"10.1371\/journal.pone.0134365","article-title":"Type 1 diabetes prone NOD mice have diminished Cxcr1 mRNA expression in polymorphonuclear neutrophils and CD4+ T lymphocytes","volume":"10","author":"Haurogn\u00e9","year":"2015","journal-title":"PLoS One"},{"issue":"1","key":"2023101106481785100_qiad085-B24","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1002\/hep.24028","article-title":"CXC chemokine receptor-1 is expressed by hepatocytes and regulates liver recovery after hepatic ischemia\/reperfusion injury","volume":"53","author":"Clarke","year":"2011","journal-title":"Hepatology"},{"issue":"4","key":"2023101106481785100_qiad085-B25","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1159\/000444125","article-title":"CXCR1 regulates pulmonary anti-pseudomonas host defense","volume":"8","author":"Carevic","year":"2016","journal-title":"J Innate Immun"},{"issue":"322","key":"2023101106481785100_qiad085-B26","doi-asserted-by":"crossref","first-page":"322ra10","DOI":"10.1126\/scitranslmed.aac7718","article-title":"CXCR1-mediated neutrophil degranulation and fungal killing promote Candida clearance and host survival","volume":"8","author":"Swamydas","year":"2016","journal-title":"Sci Transl Med"},{"issue":"2","key":"2023101106481785100_qiad085-B27","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1159\/000528780","article-title":"Modulation of neutrophil function by recombinant human IgG1 Fc hexamer in the endogenous K\/BxN mouse model of rheumatoid arthritis","volume":"108","author":"Almizraq","year":"2023","journal-title":"Pharmacology"},{"issue":"3","key":"2023101106481785100_qiad085-B28","doi-asserted-by":"crossref","first-page":"1601","DOI":"10.4049\/jimmunol.167.3.1601","article-title":"Essential role of neutrophils in the initiation and progression of a murine model of rheumatoid arthritis","volume":"167","author":"Wipke","year":"2001","journal-title":"J Immunol"},{"issue":"8","key":"2023101106481785100_qiad085-B29","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1016\/j.autrev.2009.12.013","article-title":"Neutrophils in rheumatoid arthritis: more than simple final effectors","volume":"9","author":"Casc\u00e3o","year":"2010","journal-title":"Autoimmun Rev"},{"issue":"5","key":"2023101106481785100_qiad085-B30","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1016\/j.immuni.2012.05.008","article-title":"The chemokine superfamily revisited","volume":"36","author":"Zlotnik","year":"2012","journal-title":"Immunity"},{"key":"2023101106481785100_qiad085-B31","doi-asserted-by":"crossref","first-page":"627939","DOI":"10.3389\/fimmu.2020.627939","article-title":"Editorial: role of neutrophils in inflammatory diseases","volume":"11","author":"Marichal","year":"2020","journal-title":"Front Immunol"},{"issue":"1","key":"2023101106481785100_qiad085-B32","doi-asserted-by":"crossref","first-page":"10","DOI":"10.5114\/reum.2018.74742","article-title":"Monocyte-related biomarkers of rheumatoid arthritis development in undifferentiated arthritis patients\u2014a pilot study","volume":"56","author":"Kurowska","year":"2018","journal-title":"Reumatologia"},{"key":"2023101106481785100_qiad085-B33","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1016\/j.intimp.2018.10.016","article-title":"Monocytes in rheumatoid arthritis: circulating precursors of macrophages and osteoclasts and, their heterogeneity and plasticity role in RA pathogenesis","volume":"65","author":"Rana","year":"2018","journal-title":"Int Immunopharmacol"},{"issue":"1","key":"2023101106481785100_qiad085-B34","doi-asserted-by":"crossref","first-page":"1351","DOI":"10.1038\/s41598-018-37448-z","article-title":"High percentages and activity of synovial fluid NK cells present in patients with advanced stage active rheumatoid arthritis","volume":"9","author":"Yamin","year":"2019","journal-title":"Sci Rep"},{"key":"2023101106481785100_qiad085-B35","doi-asserted-by":"crossref","first-page":"491974","DOI":"10.1100\/2012\/491974","article-title":"Natural killer cells and their role in rheumatoid arthritis: friend or foe?","volume":"2012","author":"Shegarfi","year":"2012","journal-title":"ScientificWorldJournal"},{"issue":"31","key":"2023101106481785100_qiad085-B36","doi-asserted-by":"crossref","first-page":"28663","DOI":"10.1074\/jbc.M413475200","article-title":"The CXCR1 and CXCR2 receptors form constitutive homo- and heterodimers selectively and with equal apparent affinities","volume":"280","author":"Wilson","year":"2005","journal-title":"J Biol Chem"},{"issue":"7","key":"2023101106481785100_qiad085-B37","doi-asserted-by":"crossref","first-page":"1921","DOI":"10.1002\/art.27470","article-title":"Deficiency of CXCR2, but not other chemokine receptors, attenuates autoantibody-mediated arthritis in a murine model","volume":"62","author":"Jacobs","year":"2010","journal-title":"Arthritis Rheum"},{"issue":"1","key":"2023101106481785100_qiad085-B38","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1097\/MOH.0000000000000476","article-title":"The role of CXCR2 in acute inflammatory responses and its antagonists as anti-inflammatory therapeutics","volume":"26","author":"Zhang","year":"2019","journal-title":"Curr Opin Hematol"},{"issue":"15","key":"2023101106481785100_qiad085-B39","doi-asserted-by":"crossref","first-page":"e94821","DOI":"10.1172\/jci.insight.94821","article-title":"Essential role for CCR6 in certain inflammatory diseases demonstrated using specific antagonist and knockin mice","volume":"2","author":"Robert","year":"2017","journal-title":"JCI Insight"},{"issue":"10","key":"2023101106481785100_qiad085-B40","doi-asserted-by":"crossref","first-page":"1279","DOI":"10.1038\/nbt1248","article-title":"Human C5aR knock-in mice facilitate the production and assessment of anti-inflammatory monoclonal antibodies","volume":"24","author":"Lee","year":"2006","journal-title":"Nat Biotechnol"},{"issue":"10","key":"2023101106481785100_qiad085-B41","doi-asserted-by":"crossref","first-page":"3457","DOI":"10.3390\/ijms21103457","article-title":"Two-faced roles of tumor-associated neutrophils in cancer development and progression","volume":"21","author":"Mukaida","year":"2020","journal-title":"Int J Mol Sci"},{"key":"2023101106481785100_qiad085-B42","doi-asserted-by":"crossref","first-page":"565165","DOI":"10.3389\/fimmu.2020.565165","article-title":"Neutrophil: a new player in metastatic cancers","volume":"11","author":"Wu","year":"2020","journal-title":"Front Immunol"},{"issue":"9","key":"2023101106481785100_qiad085-B43","doi-asserted-by":"crossref","first-page":"e20201342","DOI":"10.1084\/jem.20201342","article-title":"Blocking inflammation on the way: rationale for CXCR2 antagonists for the treatment of COVID-19","volume":"217","author":"Koenig","year":"2020","journal-title":"J Exp Med"},{"issue":"21","key":"2023101106481785100_qiad085-B44","doi-asserted-by":"crossref","first-page":"6735","DOI":"10.1158\/1078-0432.CCR-07-4843","article-title":"The interleukin-8 pathway in cancer","volume":"14","author":"Waugh","year":"2008","journal-title":"Clin Cancer Res"},{"issue":"2","key":"2023101106481785100_qiad085-B45","doi-asserted-by":"crossref","first-page":"812","DOI":"10.1007\/s10753-014-9991-1","article-title":"Expression of CXCR1 (interleukin-8 receptor) in murine macrophages after staphylococcus aureus infection and its possible implication on intracellular survival correlating with cytokines and bacterial anti-oxidant enzymes","volume":"38","author":"Bishayi","year":"2015","journal-title":"Inflammation"},{"key":"2023101106481785100_qiad085-B46","doi-asserted-by":"crossref","first-page":"230","DOI":"10.3389\/fncel.2018.00230","article-title":"Role of CXCR1 and interleukin-8 in methamphetamine-induced neuronal apoptosis","volume":"12","author":"Du","year":"2018","journal-title":"Front Cell Neurosci"},{"issue":"1","key":"2023101106481785100_qiad085-B47","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1002\/iid3.380","article-title":"Enhanced IgG1 -mediated antibody response towards thymus-dependent immunization in CXCR1-deficient mice","volume":"9","author":"Jaufmann","year":"2021","journal-title":"Immun Inflamm Dis"},{"issue":"5172","key":"2023101106481785100_qiad085-B48","doi-asserted-by":"crossref","first-page":"682","DOI":"10.1126\/science.8036519","article-title":"Neutrophil and B cell expansion in mice that lack the murine IL-8 receptor homolog","volume":"265","author":"Cacalano","year":"1994","journal-title":"Science"},{"issue":"10","key":"2023101106481785100_qiad085-B49","doi-asserted-by":"crossref","first-page":"1821","DOI":"10.1038\/cdd.2017.122","article-title":"An update on using CRISPR\/Cas9 in the one-cell stage mouse embryo for generating complex mutant alleles","volume":"24","author":"Kueh","year":"2017","journal-title":"Cell Death Differ"},{"issue":"9","key":"2023101106481785100_qiad085-B50","doi-asserted-by":"crossref","first-page":"e0184278","DOI":"10.1371\/journal.pone.0184278","article-title":"A fully humanized IgG-like bispecific antibody for effective dual targeting of CXCR3 and CCR6","volume":"12","author":"Robert","year":"2017","journal-title":"PLoS One"}],"container-title":["Journal of Leukocyte Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jleukbio\/advance-article-pdf\/doi\/10.1093\/jleuko\/qiad085\/51121957\/qiad085.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jleukbio\/article-pdf\/114\/4\/373\/51998193\/qiad085.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jleukbio\/article-pdf\/114\/4\/373\/51998193\/qiad085.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,12,17]],"date-time":"2023-12-17T15:16:07Z","timestamp":1702826167000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jleukbio\/article\/114\/4\/373\/7227755"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,7,21]]},"references-count":50,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2023,7,21]]},"published-print":{"date-parts":[[2023,9,27]]}},"URL":"https:\/\/doi.org\/10.1093\/jleuko\/qiad085","relation":{},"ISSN":["1938-3673"],"issn-type":[{"value":"1938-3673","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2023,10]]},"published":{"date-parts":[[2023,7,21]]}}}