{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T03:51:18Z","timestamp":1791517878992,"version":"4.3.4"},"reference-count":75,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T00:00:00Z","timestamp":1791417600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T00:00:00Z","timestamp":1791417600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["U01EB036955"],"award-info":[{"award-number":["U01EB036955"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Science"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Islet transplantation can restore glycemic control in type 1 diabetes, yet heterogeneity of immune responses and transplant outcomes necessitates improved graft monitoring. Since transplanted islets are diffusely engrafted within the liver and inaccessible to biopsy, clinical monitoring relies on blood glucose and C\u2010peptide, which change only after substantial graft injury. Here, we developed a synthetic immunological niche (IN) that captures graft\u2010associated immune responses through serial subcutaneous biopsy. We evaluated the IN across murine syngeneic, allogeneic, and autoimmune islet transplant models, including CD40\/CD154 blockade with anti\u2010CD40L. The IN identified immune populations and transcriptomic signatures reflective of the graft and distinguished syngeneic from rejecting allografts. In anti\u2010CD40L\u2010treated allografts, the IN revealed innate immune programs characterized by macrophage\u2010 and dendritic cell\u2010associated signatures linked to acceptance versus rejection, whereas untreated allografts showed stronger adaptive immune signatures. Longitudinal IN profiling detected inflammatory activation in accepted allografts, indicating persistent subclinical risk. Finally, in autoimmune allografts treated with anti\u2010CD40L plus rapamycin, IN identified a 13\u2010gene signature that separated early from late rejection and distinguished autoimmune\u2010 from alloimmune\u2010associated rejection programs. These findings establish the IN as a platform for identification of early biomarkers of islet graft rejection before overt dysfunction, addressing an unmet need in islet transplant monitoring.<\/jats:p>","DOI":"10.1002\/advs.78154","type":"journal-article","created":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T03:39:03Z","timestamp":1791517143000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Immune Biomarkers of Islet Transplant Rejection Revealed by Synthetic Immunological Niche"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8124-3121","authenticated-orcid":false,"given":"Jyotirmoy","family":"Roy","sequence":"first","affiliation":[{"name":"Department of Biomedical Engineering University of Michigan  Ann Arbor USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdalmonam Jadou","family":"Nejma","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Department of Molecular Microbiology and Immunology NextGen Precision Health Institute University of Missouri  Columbia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8829-3041","authenticated-orcid":false,"given":"Mohammad","family":"Tarique","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Department of Molecular Microbiology and Immunology NextGen Precision Health Institute University of Missouri  Columbia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-1039-8348","authenticated-orcid":false,"given":"Amod","family":"Talekar","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering University of Michigan  Ann Arbor USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-6294-5009","authenticated-orcid":false,"given":"Shengli","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Department of Molecular Microbiology and Immunology NextGen Precision Health Institute University of Missouri  Columbia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-7526-1726","authenticated-orcid":false,"given":"Brianna","family":"Ha","sequence":"additional","affiliation":[{"name":"Department of Chemical Engineering University of Michigan  Ann Arbor USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yifei","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering University of Michigan  Ann Arbor USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4312-8798","authenticated-orcid":false,"given":"Esma S.","family":"Yolcu","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Department of Molecular Microbiology and Immunology NextGen Precision Health Institute University of Missouri  Columbia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9296-9673","authenticated-orcid":false,"given":"Lonnie D.","family":"Shea","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering University of Michigan  Ann Arbor USA"},{"name":"Department of Chemical Engineering University of Michigan  Ann Arbor USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,8]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2024.1391504","article-title":"Pancreatic Islet Transplantation: Current Advances and Challenges","volume":"15","author":"Wang Q.","year":"2024","journal-title":"Frontiers in immunology"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11892\u2010017\u20100847\u20106"},{"key":"e_1_2_10_4_1","doi-asserted-by":"crossref","first-page":"1068","DOI":"10.2337\/db25-0037","article-title":"Advances in Cell Replacement Therapies for Diabetes","volume":"74","author":"Hering B. 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F.","year":"2021","journal-title":"American Journal of Transplantation"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc21\u20102688"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1455691"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/ajt.15339"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2021091191"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aba2501"},{"key":"e_1_2_10_17_1","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pmed.1002286","article-title":"Graft\u2010derived Cell\u2010free DNA, a Noninvasive Early Rejection and Graft Damage Marker in Liver Transplantation: A Prospective, Observational, Multicenter Cohort Study","volume":"14","author":"Sch\u00fctz E.","year":"2017","journal-title":"PLOS Medicine"},{"key":"e_1_2_10_18_1","doi-asserted-by":"crossref","first-page":"1783","DOI":"10.3390\/cells13211783","article-title":"Islet Transplantation: Current Limitations and Challenges for Successful Outcomes","volume":"13","author":"Langlois A.","year":"2024","journal-title":"Cells"},{"key":"e_1_2_10_19_1","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1007\/s11892-018-1059-4","article-title":"Biomarkers in Islet Cell Transplantation for Type 1 Diabetes","volume":"18","author":"AlRashidi F. 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L.","year":"2026","journal-title":"Science Advances"},{"key":"e_1_2_10_25_1","doi-asserted-by":"crossref","unstructured":"J.Roy Y.Jiang andR.Mao \u201cSynthetic Immunological Niche Reveals Early Immune Dysregulation and Stratifies Therapeutic Response in Type 1 Diabetes \u201d preprint bioRxiv (2026) https:\/\/doi.org\/10.64898\/2026.03.06.710219.","DOI":"10.64898\/2026.03.06.710219"},{"key":"e_1_2_10_26_1","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1038\/s41392-024-02050-5","article-title":"Tissue\u2010resident immune cells: From defining characteristics to roles in diseases","volume":"10","author":"Li J.","year":"2025","journal-title":"Signal Transduction and Targeted Therapy"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev\u2010immunol\u2010093019\u2010112809"},{"key":"e_1_2_10_28_1","doi-asserted-by":"crossref","first-page":"S224","DOI":"10.1016\/j.ajt.2025.07.493","article-title":"CD40L Co\u2010Stimulation Blockade as a Non\u2010Toxic Calcineurin Inhibitor\u2010Free Immunosuppression for Beta Cell Replacement Therapy: Preliminary Results From a Pilot Clinical Study","volume":"25","author":"Wojcik N.","year":"2025","journal-title":"American Journal of Transplantation"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.tp.0000542553.72347.f7"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/gene.2015.29"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneuroim.2018.11.013"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.aea2960"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20210116"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.886225"},{"key":"e_1_2_10_35_1","doi-asserted-by":"crossref","DOI":"10.1126\/science.adp0714","article-title":"Hepatic leukemia factor directs tissue residency of proinflammatory memory CD4+ T cells","volume":"390","author":"Kiuchi M.","year":"2025","journal-title":"Science"},{"key":"e_1_2_10_36_1","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2022.853349","article-title":"Single\u2010Cell Landscape of Mouse Islet Allograft and Syngeneic Graft","volume":"13","author":"Chen P.","year":"2022","journal-title":"Frontiers in Immunology"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2020.107579"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365\u20102567.2009.03091.x"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI97945"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010024\u201048360\u20108"},{"key":"e_1_2_10_41_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.xinn.2025.101005","article-title":"IFI30 promotes Tumor\u2010associated Macrophage Infiltration via Activation of the ATF3\u2010CCL5 Axis in Breast Cancer","volume":"6","author":"Ren L.","year":"2025","journal-title":"The Innovation"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0903869"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2208522119"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2012.04.024"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cytogfr.2007.04.002"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.1096\/fasebj.13.15.2125"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.1005551"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2008.080081"},{"key":"e_1_2_10_49_1","doi-asserted-by":"crossref","first-page":"1781","DOI":"10.1056\/NEJMoa1214514","article-title":"Oncogenic CSF3R Mutations in Chronic Neutrophilic Leukemia and Atypical CML","volume":"368","author":"Maxson J. 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