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Thus, the perinatal period offers a suitable time window for disease prevention. Moreover, thymic selection of autoreactive T cells is most active during this period, providing a therapeutic opportunity not exploited to date. We therefore devised a strategy by which the T1D-triggering antigen preproinsulin fused with the immunoglobulin (Ig)G Fc fragment (PPI-Fc) is delivered to fetuses through the neonatal Fc receptor (FcRn) pathway, which physiologically transfers maternal IgGs through the placenta. PPI-Fc administered to pregnant PPIB15\u201323 T-cell receptor\u2013transgenic mice efficiently accumulated in fetuses through the placental FcRn and protected them from subsequent diabetes development. Protection relied on ferrying of PPI-Fc to the thymus by migratory dendritic cells and resulted in a rise in thymic-derived CD4+ regulatory T cells expressing transforming growth factor-\u03b2 and in increased effector CD8+ T cells displaying impaired cytotoxicity. Moreover, polyclonal splenocytes from nonobese diabetic (NOD) mice transplacentally treated with PPI-Fc were less diabetogenic upon transfer into NOD.scid recipients. Transplacental antigen vaccination provides a novel strategy for early T1D prevention and, further, is applicable to other immune-mediated conditions.<\/jats:p>","DOI":"10.2337\/db15-0024","type":"journal-article","created":{"date-parts":[[2015,4,28]],"date-time":"2015-04-28T02:32:16Z","timestamp":1430188336000},"page":"3532-3542","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":32,"title":["Materno-Fetal Transfer of Preproinsulin Through the Neonatal Fc Receptor Prevents Autoimmune Diabetes"],"prefix":"10.2337","volume":"64","author":[{"given":"Slobodan","family":"Culina","sequence":"first","affiliation":[{"name":"INSERM, U1016, Cochin Institute, Paris, France"},{"name":"CNRS, UMR 8104, Cochin Institute, Paris, France"},{"name":"Paris Descartes University, Sorbonne Paris Cit\u00e9, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nimesh","family":"Gupta","sequence":"additional","affiliation":[{"name":"INSERM, UMRS 1138, Les Cordeliers Research Center, Paris, France"},{"name":"Pierre et Marie Curie-Paris 6 University, Sorbonne Universities, UMRS 1138, Paris, France"},{"name":"Paris Descartes University, UMRS 1138, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raphael","family":"Boisgard","sequence":"additional","affiliation":[{"name":"CEA\/DSV\/I2BM\/SHFJ\/U1023, Laboratory of Experimental Molecular Imaging, Orsay, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georgia","family":"Afonso","sequence":"additional","affiliation":[{"name":"INSERM, U1016, Cochin Institute, Paris, France"},{"name":"CNRS, UMR 8104, Cochin Institute, Paris, France"},{"name":"Paris Descartes University, Sorbonne Paris Cit\u00e9, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie-Claude","family":"Gagnerault","sequence":"additional","affiliation":[{"name":"INSERM, U1016, Cochin Institute, Paris, France"},{"name":"CNRS, UMR 8104, Cochin Institute, Paris, France"},{"name":"Paris Descartes University, Sorbonne Paris Cit\u00e9, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jordan","family":"Dimitrov","sequence":"additional","affiliation":[{"name":"INSERM, UMRS 1138, Les Cordeliers Research Center, Paris, France"},{"name":"Pierre et Marie Curie-Paris 6 University, Sorbonne Universities, UMRS 1138, Paris, France"},{"name":"Paris Descartes University, UMRS 1138, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"\u00d8sterbye","sequence":"additional","affiliation":[{"name":"Department of International Health, Immunology and Microbiology, Panum Institute, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sune","family":"Justesen","sequence":"additional","affiliation":[{"name":"Department of International Health, Immunology and Microbiology, Panum Institute, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandrine","family":"Luce","sequence":"additional","affiliation":[{"name":"INSERM, U1016, Cochin Institute, Paris, France"},{"name":"CNRS, UMR 8104, Cochin Institute, Paris, France"},{"name":"Paris Descartes University, Sorbonne Paris Cit\u00e9, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mikha\u00ebl","family":"Attias","sequence":"additional","affiliation":[{"name":"INSERM, U1016, Cochin Institute, Paris, France"},{"name":"CNRS, UMR 8104, Cochin Institute, Paris, France"},{"name":"Paris Descartes University, Sorbonne Paris Cit\u00e9, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruno","family":"Kyewski","sequence":"additional","affiliation":[{"name":"Division of Developmental Immunology, DKFZ, Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S\u00f8ren","family":"Buus","sequence":"additional","affiliation":[{"name":"Department of International Health, Immunology and Microbiology, Panum Institute, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F. 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