{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T01:27:43Z","timestamp":1788917263465,"version":"build-2803163510"},"reference-count":50,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,1,19]],"date-time":"2026-01-19T00:00:00Z","timestamp":1768780800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002915","name":"Fondation pour la Recherche M\u00e9dicale","doi-asserted-by":"publisher","award":["EQU201903007853"],"award-info":[{"award-number":["EQU201903007853"]}],"id":[{"id":"10.13039\/501100002915","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009516","name":"Universit\u00e9 Sorbonne Paris Cit\u00e9","doi-asserted-by":"crossref","award":["TolNP"],"award-info":[{"award-number":["TolNP"]}],"id":[{"id":"10.13039\/501100009516","id-type":"DOI","asserted-by":"crossref"}]},{"name":"EFSD\/Novo Nordisk A\/S"},{"name":"INSERM, INSERM-Transfert"},{"name":"Universit\u00e9 Paris Cit\u00e9"},{"name":"Universit\u00e9 Sorbonne Paris Nord"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Autoimmune type 1 diabetes (T1D) results from the failure of the physiologic regulatory mechanisms that are designed to maintain immune tolerance to pancreatic beta cells. Consequently, the design of strategies to restore tolerance to beta cell antigens is an attractive objective of translational research. We have designed ultrasmall nanoparticles (NPs) loaded with a proinsulin (PI) fusion protein and an agonist for the aryl hydrocarbon receptor (AhR), a transcription factor promoting tolerance induction by different immune cells. We report that a 4 week-treatment with these NPs in non-obese diabetic (NOD) mice starting at disease onset induces temporary and sometimes durable disease remission. Mechanistically, short-term NP treatment induces a rapid depletion of islet infiltrates with a dramatic reduction in the number of CD8+ T cells and dendritic cells. This is accompanied by the emergence of B lymphocytes producing IL-10. In the rare mice that undergo durable disease remission, the disappearance of islet infiltrates is associated with the emergence of Foxp3+ CD4+ regulatory T cells, IFN-\u03b3-producing memory T cells in the spleen, and draining lymph nodes (LNs). We conclude that treatment with these NPs could be of interest in the treatment of recent-onset autoimmune diabetes, but is unlikely to be sufficient for the induction of long-term remission as a stand-alone therapy.<\/jats:p>","DOI":"10.3390\/cells15020174","type":"journal-article","created":{"date-parts":[[2026,1,19]],"date-time":"2026-01-19T09:57:02Z","timestamp":1768816622000},"page":"174","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Proinsulin-Loaded Nanoparticles Suppress Insulitis and Induce Temporary Diabetes Remission"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-6268-7286","authenticated-orcid":false,"given":"Maeva","family":"Agapoff","sequence":"first","affiliation":[{"name":"Institut Necker Enfants Malades, Universit\u00e9 Paris Cit\u00e9, INSERM, CNRS, F-75015 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chlo\u00e9","family":"Dubreil","sequence":"additional","affiliation":[{"name":"Institut Necker Enfants Malades, Universit\u00e9 Paris Cit\u00e9, INSERM, CNRS, F-75015 Paris, France"},{"name":"Universit\u00e9 Sorbonne Paris Nord and Universit\u00e9 Paris Cit\u00e9, INSERM, LVTS, F-75018 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emmanuelle","family":"Waeckel-\u00c9n\u00e9e","sequence":"additional","affiliation":[{"name":"Institut Necker Enfants Malades, Universit\u00e9 Paris Cit\u00e9, INSERM, CNRS, F-75015 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7688-0177","authenticated-orcid":false,"given":"Fr\u00e9d\u00e9ric","family":"Geinguenaud","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Sorbonne Paris Nord and Universit\u00e9 Paris Cit\u00e9, INSERM, LVTS, F-75018 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Val\u00e9rie","family":"Manceau","sequence":"additional","affiliation":[{"name":"Institut Necker Enfants Malades, Universit\u00e9 Paris Cit\u00e9, INSERM, CNRS, F-75015 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7542-042X","authenticated-orcid":false,"given":"Julien","family":"Diana","sequence":"additional","affiliation":[{"name":"Institut Necker Enfants Malades, Universit\u00e9 Paris Cit\u00e9, INSERM, CNRS, F-75015 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3653-3576","authenticated-orcid":false,"given":"Barbara","family":"Bertocci","sequence":"additional","affiliation":[{"name":"Institut Necker Enfants Malades, Universit\u00e9 Paris Cit\u00e9, INSERM, CNRS, F-75015 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6129-539X","authenticated-orcid":false,"given":"Laurence","family":"Motte","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Sorbonne Paris Nord and Universit\u00e9 Paris Cit\u00e9, INSERM, LVTS, F-75018 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3782-0750","authenticated-orcid":false,"given":"Peter","family":"van Endert","sequence":"additional","affiliation":[{"name":"Institut Necker Enfants Malades, Universit\u00e9 Paris Cit\u00e9, INSERM, CNRS, F-75015 Paris, France"},{"name":"Service Immunologie Biologique, AP-HP, H\u00f4pital Universitaire Necker-Enfants Malades, F-75015 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1007\/s00125-017-4530-x","article-title":"Hope vs. hype: Where are we in type 1 diabetes?","volume":"61","author":"Skyler","year":"2018","journal-title":"Diabetologia"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"510","DOI":"10.1126\/science.abh1654","article-title":"Immunotherapy: Building a bridge to a cure for type 1 diabetes","volume":"373","author":"Bluestone","year":"2021","journal-title":"Science"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1016\/j.immuni.2010.04.003","article-title":"The long and winding road to understanding and conquering type 1 diabetes","volume":"32","author":"Santamaria","year":"2010","journal-title":"Immunity"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1016\/j.immuni.2010.04.001","article-title":"Etiology of type 1 diabetes","volume":"32","author":"Todd","year":"2010","journal-title":"Immunity"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"746","DOI":"10.1016\/j.coi.2011.10.001","article-title":"Diabetogenic T lymphocytes in human Type 1 diabetes","volume":"23","author":"Roep","year":"2011","journal-title":"Curr. 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