{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T05:26:47Z","timestamp":1787808407535,"version":"build-2784847793"},"reference-count":48,"publisher":"American Society for Clinical Investigation","issue":"6","license":[{"start":{"date-parts":[[2022,3,22]],"date-time":"2022-03-22T00:00:00Z","timestamp":1647907200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Johns Hopkins All Children\u2019s Foundation IRG Program","award":["No grant\/fund number."],"award-info":[{"award-number":["No grant\/fund number."]}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"crossref","award":["431549029\u2013SFB 1451,EXC 2030\u2013390661388,411422114-GRK 2550"],"award-info":[{"award-number":["431549029\u2013SFB 1451,EXC 2030\u2013390661388,411422114-GRK 2550"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82071326"],"award-info":[{"award-number":["82071326"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,3,22]]},"abstract":"<jats:sec>\n                    <jats:title>BACKGROUND<\/jats:title>\n                    <jats:p>\n                      Pathophysiology of type 1 diabetes (T1D) is illustrated by pancreatic islet infiltration of inflammatory lymphocytes, including CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cells; however, the molecular factors mediating their recruitment remain unknown. We hypothesized that single-cell RNA-sequencing (scRNA-Seq) analysis of immune cell populations isolated from islets of NOD mice captured gene expression dynamics providing critical insight into autoimmune diabetes pathogenesis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>\n                      Pancreatic sections from human donors were investigated, including individuals with T1D, autoantibody-positive (aAb\n                      <jats:sup>+<\/jats:sup>\n                      ) individuals, and individuals without diabetes who served as controls. IHC was performed to assess islet hormones and both novel and canonical immune cell markers that were identified from unbiased, state-of-the-art workflows after reanalyzing murine scRNA-Seq data sets.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      Computational workflows identified cell adhesion molecule 1\u2013mediated (\n                      <jats:italic>Cadm1<\/jats:italic>\n                      -mediated) homotypic binding among the most important intercellular interactions among all cell clusters, as well as\n                      <jats:italic>Cadm1<\/jats:italic>\n                      enrichment in macrophages and DCs from pancreata of NOD mice. Immunostaining of human pancreata revealed an increased number of CADM1\n                      <jats:sup>+<\/jats:sup>\n                      glucagon\n                      <jats:sup>+<\/jats:sup>\n                      cells adjacent to CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cells in sections from T1D and aAb\n                      <jats:sup>+<\/jats:sup>\n                      donors compared with individuals without diabetes. Numbers of CADM1\n                      <jats:sup>+<\/jats:sup>\n                      CD68\n                      <jats:sup>+<\/jats:sup>\n                      peri-islet myeloid cells adjacent to CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cells were also increased in pancreatic sections from both T1D and aAb\n                      <jats:sup>+<\/jats:sup>\n                      donors compared with individuals without diabetes.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSION<\/jats:title>\n                    <jats:p>\n                      Increased detection of CADM1\n                      <jats:sup>+<\/jats:sup>\n                      cells adjacent to CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cells in pancreatic sections of individuals with T1D and those who were aAb\n                      <jats:sup>+<\/jats:sup>\n                      validated workflows and indicated CADM1-mediated intercellular contact may facilitate islet infiltration of cytotoxic T lymphocytes and serve as a potential therapeutic target for preventing T1D pathogenesis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>FUNDING<\/jats:title>\n                    <jats:p>The Johns Hopkins All Children\u2019s Foundation Institutional Research Grant Program, the National Natural Science Foundation of China (grant 82071326), and the Deutsche Forschungsgemeinschaft (grants 431549029\u2013SFB1451, EXC2030\u2013390661388, and 411422114-GRK2550).<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1172\/jci.insight.153136","type":"journal-article","created":{"date-parts":[[2022,2,8]],"date-time":"2022-02-08T12:03:26Z","timestamp":1644321806000},"source":"Crossref","is-referenced-by-count":23,"title":["Evidence of islet CADM1-mediated immune cell interactions during 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