{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T03:17:48Z","timestamp":1772507868565,"version":"3.50.1"},"posted":{"date-parts":[[2024,7,19]]},"group-title":"Immunology","reference-count":97,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2024,7,19]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:sec>\n                  <jats:title>Aims\/hypothesis<\/jats:title>\n                  <jats:p>\n                    Immunotherapeutics targeting T cells are crucial for inhibiting autoimmune disease progression proximal to disease onset in type 1 diabetes. A growing number of T cell-directed therapeutics have demonstrated partial therapeutic efficacy, with anti-CD3 (\u03b1-CD3) representing the only regulatory agency-approved drug capable of slowing disease progression through a mechanism involving the induction of partial T cell exhaustion. There is an outstanding need to augment the durability and effectiveness of T cell targeting by directly restraining proinflammatory T helper type 1 (Th1) and type 1 cytotoxic CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cell (Tc1) subsets, while simultaneously augmenting regulatory T cell (Treg) activity. Here, we present a novel strategy for reducing diabetes incidence in the NOD mouse model using a blocking monoclonal antibody targeting the type 1 diabetes-risk associated T cell co-stimulatory receptor, CD226.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Female NOD mice were treated with anti-CD226 between 7-8 weeks of age and then monitored for diabetes incidence and therapeutic mechanism of action.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>\n                    Compared to isotype-treated controls, anti-CD226 treated NOD mice showed reduced insulitis severity at 12 weeks and decreased disease incidence at 30 weeks. Flow cytometric analysis performed five weeks post-treatment demonstrated reduced proliferation of CD4\n                    <jats:sup>+<\/jats:sup>\n                    and CD8\n                    <jats:sup>+<\/jats:sup>\n                    effector memory T cells in spleens of anti-CD226 treated mice. Phenotyping of pancreatic Tregs revealed increased CD25 expression and STAT5 phosphorylation following anti-CD226, with splenic Tregs displaying augmented suppression of CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cell responders\n                    <jats:italic>in vitro.<\/jats:italic>\n                    Anti-CD226 treated mice exhibited reduced frequencies of islet-specific glucose-6-phosphatase catalytic subunit related protein (IGRP)-reactive CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells in the pancreas, using both\n                    <jats:italic>ex vivo<\/jats:italic>\n                    tetramer staining and single-cell T cell receptor sequencing (scTCR-seq) approaches.\n                    <jats:sup>51<\/jats:sup>\n                    Cr-release assays demonstrated reduced cell-mediated lysis of beta-cells by anti-CD226-treated autoreactive cytotoxic T lymphocytes.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusions\/interpretation<\/jats:title>\n                  <jats:p>CD226 blockade reduces T cell cytotoxicity and improves Treg function, representing a targeted and rational approach for restoring immune regulation in type 1 diabetes.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Research in Context<\/jats:title>\n                  <jats:sec>\n                    <jats:title>What is already known about this subject?<\/jats:title>\n                    <jats:list list-type=\"bullet\">\n                      <jats:list-item>\n                        <jats:p>The co-stimulatory receptor CD226 is upregulated upon activation and is highly expressed on NK cell subsets, myeloid cells, and effector T cells.<\/jats:p>\n                      <\/jats:list-item>\n                      <jats:list-item>\n                        <jats:p>\n                          A single nucleotide polymorphism in CD226 (\n                          <jats:italic>rs763361<\/jats:italic>\n                          ; C&gt;T) results in a Gly307Ser missense mutation linked to genetic susceptibility for type 1 diabetes.\n                        <\/jats:p>\n                      <\/jats:list-item>\n                      <jats:list-item>\n                        <jats:p>\n                          Global knockout of\n                          <jats:italic>Cd226<\/jats:italic>\n                          and conditional\n                          <jats:italic>Cd226<\/jats:italic>\n                          knockout in FoxP3\n                          <jats:sup>+<\/jats:sup>\n                          Tregs reduced insulitis severity and diabetes incidence in NOD mice, indicating a crucial role for CD226 in disease pathogenesis.\n                        <\/jats:p>\n                      <\/jats:list-item>\n                    <\/jats:list>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>What is the key question?<\/jats:title>\n                    <jats:list list-type=\"bullet\">\n                      <jats:list-item>\n                        <jats:p>Can CD226 blockade reduce T cell cytotoxicity and improve Treg function to diminish diabetes incidence in NOD mice?<\/jats:p>\n                      <\/jats:list-item>\n                    <\/jats:list>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>What are the new findings?<\/jats:title>\n                    <jats:list list-type=\"bullet\">\n                      <jats:list-item>\n                        <jats:p>\n                          Anti-CD226 treatment reduced insulitis, decreased disease incidence, and inhibited splenic CD4\n                          <jats:sup>+<\/jats:sup>\n                          and CD8\n                          <jats:sup>+<\/jats:sup>\n                          effector memory T cell proliferation.\n                        <\/jats:p>\n                      <\/jats:list-item>\n                      <jats:list-item>\n                        <jats:p>\n                          Pancreatic Tregs from anti-CD226 treated mice exhibited increased CD25 expression; splenic Tregs displayed augmented STAT5 phosphorylation and suppressive capacity\n                          <jats:italic>in vitro<\/jats:italic>\n                          .\n                        <\/jats:p>\n                      <\/jats:list-item>\n                      <jats:list-item>\n                        <jats:p>\n                          Anti-CD226 treatment reduced IGRP-specific pancreatic CD8\n                          <jats:sup>+<\/jats:sup>\n                          T cell frequencies, and reduced autoreactive CD8\n                          <jats:sup>+<\/jats:sup>\n                          T cell-mediated lysis of beta-cells\n                          <jats:italic>in vitro<\/jats:italic>\n                          .\n                        <\/jats:p>\n                      <\/jats:list-item>\n                    <\/jats:list>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>How might this impact on clinical practice in the foreseeable future?<\/jats:title>\n                    <jats:list list-type=\"bullet\">\n                      <jats:list-item>\n                        <jats:p>CD226 blockade could reduce autoreactive T cell cytotoxicity, enhance Treg function, and slow disease progression in high-risk or recent-onset type 1 diabetes cases.<\/jats:p>\n                      <\/jats:list-item>\n                    <\/jats:list>\n                  <\/jats:sec>\n                <\/jats:sec>","DOI":"10.1101\/2024.07.16.603756","type":"posted-content","created":{"date-parts":[[2024,7,19]],"date-time":"2024-07-19T21:20:11Z","timestamp":1721424011000},"source":"Crossref","is-referenced-by-count":2,"title":["Inhibition of CD226 Co-Stimulation Suppresses Diabetes Development in the NOD Mouse by Augmenting Tregs and Diminishing Effector T Cell Function"],"prefix":"10.64898","author":[{"given":"Matthew E.","family":"Brown","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Puchong","family":"Thirawatananond","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leeana D.","family":"Peters","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elizabeth J.","family":"Kern","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sonali","family":"Vijay","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lindsey K.","family":"Sachs","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9491-0958","authenticated-orcid":false,"given":"Amanda L.","family":"Posgai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maigan A.","family":"Brusko","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Melanie R.","family":"Shapiro","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8817-6355","authenticated-orcid":false,"given":"Clayton E.","family":"Mathews","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5787-476X","authenticated-orcid":false,"given":"Rhonda","family":"Bacher","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Todd M.","family":"Brusko","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2024072322300516000_2024.07.16.603756v1.1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.667989"},{"key":"2024072322300516000_2024.07.16.603756v1.2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(13)60591-7"},{"key":"2024072322300516000_2024.07.16.603756v1.3","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1902226"},{"key":"2024072322300516000_2024.07.16.603756v1.4","doi-asserted-by":"publisher","DOI":"10.2337\/db13-0345"},{"key":"2024072322300516000_2024.07.16.603756v1.5","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2212728"},{"key":"2024072322300516000_2024.07.16.603756v1.6","doi-asserted-by":"publisher","DOI":"10.1111\/j.1742-7843.2009.00452.x"},{"key":"2024072322300516000_2024.07.16.603756v1.7","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1403046"},{"key":"2024072322300516000_2024.07.16.603756v1.8","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1402381"},{"key":"2024072322300516000_2024.07.16.603756v1.9","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M113.498253"},{"key":"2024072322300516000_2024.07.16.603756v1.10","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1103627"},{"key":"2024072322300516000_2024.07.16.603756v1.11","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20150792"},{"key":"2024072322300516000_2024.07.16.603756v1.12","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1300945"},{"key":"2024072322300516000_2024.07.16.603756v1.13","doi-asserted-by":"publisher","DOI":"10.1159\/000488182"},{"key":"2024072322300516000_2024.07.16.603756v1.14","doi-asserted-by":"publisher","DOI":"10.1016\/j.humimm.2012.10.009"},{"key":"2024072322300516000_2024.07.16.603756v1.15","doi-asserted-by":"publisher","DOI":"10.1111\/imcb.12438"},{"key":"2024072322300516000_2024.07.16.603756v1.16","doi-asserted-by":"publisher","DOI":"10.1126\/scisignal.aar3083"},{"key":"2024072322300516000_2024.07.16.603756v1.17","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20030958"},{"key":"2024072322300516000_2024.07.16.603756v1.18","doi-asserted-by":"publisher","DOI":"10.1093\/intimm\/dxh199"},{"key":"2024072322300516000_2024.07.16.603756v1.19","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.54.9.2820"},{"key":"2024072322300516000_2024.07.16.603756v1.20","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.02180"},{"key":"2024072322300516000_2024.07.16.603756v1.21","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.01883"},{"key":"2024072322300516000_2024.07.16.603756v1.22","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.7834"},{"key":"2024072322300516000_2024.07.16.603756v1.23","doi-asserted-by":"publisher","DOI":"10.2337\/db23-0307"},{"key":"2024072322300516000_2024.07.16.603756v1.24","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20080707"},{"key":"2024072322300516000_2024.07.16.603756v1.25","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1602037"},{"key":"2024072322300516000_2024.07.16.603756v1.26","unstructured":"National Research Council. Committee for the Update of the Guide for the C, Use of Laboratory A, Institute for Laboratory Animal R, National Academies P (2011) Guide for the care and use of laboratory animals. 8th edn. National Academies Press, Washington, D.C."},{"key":"2024072322300516000_2024.07.16.603756v1.27","doi-asserted-by":"publisher","DOI":"10.2337\/db15-0164"},{"key":"2024072322300516000_2024.07.16.603756v1.28","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.171.7.3435"},{"key":"2024072322300516000_2024.07.16.603756v1.29","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.173.11.6777"},{"key":"2024072322300516000_2024.07.16.603756v1.30","doi-asserted-by":"publisher","DOI":"10.1016\/j.jim.2008.09.014"},{"key":"2024072322300516000_2024.07.16.603756v1.31","doi-asserted-by":"publisher","DOI":"10.3791\/2724"},{"key":"2024072322300516000_2024.07.16.603756v1.32","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1400997"},{"key":"2024072322300516000_2024.07.16.603756v1.33","doi-asserted-by":"publisher","DOI":"10.2337\/diab.40.7.842"},{"key":"2024072322300516000_2024.07.16.603756v1.34","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bts635"},{"key":"2024072322300516000_2024.07.16.603756v1.35","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-021-02584-9"},{"key":"2024072322300516000_2024.07.16.603756v1.36","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btaa1009"},{"key":"2024072322300516000_2024.07.16.603756v1.37","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-0933-9"},{"key":"2024072322300516000_2024.07.16.603756v1.38","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.4295"},{"key":"2024072322300516000_2024.07.16.603756v1.39","doi-asserted-by":"publisher","DOI":"10.26508\/lsa.202201503"},{"key":"2024072322300516000_2024.07.16.603756v1.40","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-023-01767-y"},{"key":"2024072322300516000_2024.07.16.603756v1.41","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-29356-8"},{"key":"2024072322300516000_2024.07.16.603756v1.42","doi-asserted-by":"publisher","DOI":"10.1016\/j.cels.2019.03.003"},{"key":"2024072322300516000_2024.07.16.603756v1.43","doi-asserted-by":"crossref","unstructured":"Korsunsky I , Nathan A , Millard N , Raychaudhuri S (2019) Presto scales Wilcoxon and auROC analyses to millions of observations. In, BioRxiv","DOI":"10.1101\/653253"},{"key":"2024072322300516000_2024.07.16.603756v1.44","doi-asserted-by":"publisher","DOI":"10.12688\/f1000research.8987.2"},{"key":"2024072322300516000_2024.07.16.603756v1.45","doi-asserted-by":"publisher","DOI":"10.1038\/s41592-019-0654-x"},{"key":"2024072322300516000_2024.07.16.603756v1.46","doi-asserted-by":"publisher","DOI":"10.12688\/f1000research.22139.2"},{"key":"2024072322300516000_2024.07.16.603756v1.47","first-page":"70","article-title":"Biostrings: Efficient manipulation of biological strings","volume":"2","year":"2024","journal-title":"In. R package version"},{"key":"2024072322300516000_2024.07.16.603756v1.48","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btaa1011"},{"key":"2024072322300516000_2024.07.16.603756v1.49","unstructured":"Blighe K , Rana S , Lewis M (2023) EnhancedVolcano: Publication-ready volcano plots with enhanced colouring and labeling. In. R package version 1.20.0"},{"key":"2024072322300516000_2024.07.16.603756v1.50","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4939-3139-2_4"},{"key":"2024072322300516000_2024.07.16.603756v1.51","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.873560"},{"key":"2024072322300516000_2024.07.16.603756v1.52","doi-asserted-by":"publisher","DOI":"10.1038\/s41423-020-00599-z"},{"key":"2024072322300516000_2024.07.16.603756v1.53","doi-asserted-by":"publisher","DOI":"10.1126\/science.abh1657"},{"key":"2024072322300516000_2024.07.16.603756v1.54","doi-asserted-by":"publisher","DOI":"10.1093\/intimm\/dxh059"},{"key":"2024072322300516000_2024.07.16.603756v1.55","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2022.02.005"},{"key":"2024072322300516000_2024.07.16.603756v1.56","doi-asserted-by":"publisher","DOI":"10.1111\/j.0105-2896.2010.00907.x"},{"key":"2024072322300516000_2024.07.16.603756v1.57","doi-asserted-by":"publisher","DOI":"10.1038\/s41388-020-1237-0"},{"key":"2024072322300516000_2024.07.16.603756v1.58","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.88242"},{"key":"2024072322300516000_2024.07.16.603756v1.59","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-03552-w"},{"key":"2024072322300516000_2024.07.16.603756v1.60","doi-asserted-by":"publisher","DOI":"10.2337\/db17-0666"},{"key":"2024072322300516000_2024.07.16.603756v1.61","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.838484"},{"key":"2024072322300516000_2024.07.16.603756v1.62","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20081752"},{"key":"2024072322300516000_2024.07.16.603756v1.63","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1423769112"},{"key":"2024072322300516000_2024.07.16.603756v1.64","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2016.01.021"},{"key":"2024072322300516000_2024.07.16.603756v1.65","doi-asserted-by":"publisher","DOI":"10.1093\/intimm\/dxz067"},{"key":"2024072322300516000_2024.07.16.603756v1.66","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-26099-w"},{"key":"2024072322300516000_2024.07.16.603756v1.67","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2249.2007.03370.x"},{"key":"2024072322300516000_2024.07.16.603756v1.68","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1900052"},{"key":"2024072322300516000_2024.07.16.603756v1.69","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M300702200"},{"key":"2024072322300516000_2024.07.16.603756v1.70","doi-asserted-by":"publisher","DOI":"10.1016\/S0024-3205(03)00606-4"},{"key":"2024072322300516000_2024.07.16.603756v1.71","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2014.10.018"},{"key":"2024072322300516000_2024.07.16.603756v1.72","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2012.10.017"},{"key":"2024072322300516000_2024.07.16.603756v1.73","doi-asserted-by":"publisher","DOI":"10.1038\/srep44661"},{"key":"2024072322300516000_2024.07.16.603756v1.74","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0049213"},{"key":"2024072322300516000_2024.07.16.603756v1.75","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.624568"},{"key":"2024072322300516000_2024.07.16.603756v1.76","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2019.07.065"},{"key":"2024072322300516000_2024.07.16.603756v1.77","doi-asserted-by":"publisher","DOI":"10.1093\/abbs\/gmp018"},{"key":"2024072322300516000_2024.07.16.603756v1.78","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.02537"},{"key":"2024072322300516000_2024.07.16.603756v1.79","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2014.02.038"},{"key":"2024072322300516000_2024.07.16.603756v1.80","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1814052115"},{"key":"2024072322300516000_2024.07.16.603756v1.81","doi-asserted-by":"publisher","DOI":"10.1038\/ni.1884"},{"key":"2024072322300516000_2024.07.16.603756v1.82","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-08960-1"},{"key":"2024072322300516000_2024.07.16.603756v1.83","doi-asserted-by":"publisher","DOI":"10.1093\/intimm\/dxn002"},{"key":"2024072322300516000_2024.07.16.603756v1.84","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-017-4377-1"},{"key":"2024072322300516000_2024.07.16.603756v1.85","doi-asserted-by":"publisher","DOI":"10.1038\/nri2889"},{"key":"2024072322300516000_2024.07.16.603756v1.86","doi-asserted-by":"publisher","DOI":"10.1016\/j.coph.2018.05.010"},{"key":"2024072322300516000_2024.07.16.603756v1.87","doi-asserted-by":"publisher","DOI":"10.1038\/sj.leu.2404683"},{"key":"2024072322300516000_2024.07.16.603756v1.88","doi-asserted-by":"publisher","DOI":"10.2337\/dc18-0494"},{"key":"2024072322300516000_2024.07.16.603756v1.89","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.161812"},{"key":"2024072322300516000_2024.07.16.603756v1.90","doi-asserted-by":"publisher","DOI":"10.1111\/trf.14841"},{"key":"2024072322300516000_2024.07.16.603756v1.91","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.aai7793"},{"key":"2024072322300516000_2024.07.16.603756v1.92","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellimm.2017.07.007"},{"key":"2024072322300516000_2024.07.16.603756v1.93","doi-asserted-by":"publisher","DOI":"10.1084\/jem.161.5.1063"},{"issue":"23","key":"2024072322300516000_2024.07.16.603756v1.94","doi-asserted-by":"crossref","first-page":"13475","DOI":"10.1016\/S0021-9258(18)80021-7","article-title":"Characterization of a novel membrane glycoprotein involved in platelet activation","volume":"264","year":"1989","journal-title":"J Biol Chem"},{"key":"2024072322300516000_2024.07.16.603756v1.95","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20032206"},{"key":"2024072322300516000_2024.07.16.603756v1.96","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0609.2004.00345.x"},{"key":"2024072322300516000_2024.07.16.603756v1.97","doi-asserted-by":"publisher","DOI":"10.1177\/0963689720939127"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1101\/2024.07.16.603756","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T06:44:05Z","timestamp":1768459445000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.1101\/2024.07.16.603756"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,7,19]]},"references-count":97,"URL":"https:\/\/doi.org\/10.1101\/2024.07.16.603756","relation":{},"subject":[],"published":{"date-parts":[[2024,7,19]]},"subtype":"preprint"}}