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Article Dans Une Revue Diabetes Année : 2015

Materno-Fetal Transfer of Preproinsulin Through the Neonatal Fc Receptor Prevents Autoimmune Diabetes

Slobodan Culina
Nimesh Gupta
  • Fonction : Auteur
Raphael Boisgard
  • Fonction : Auteur
Georgia Afonso
  • Fonction : Auteur
Marie-Claude Gagnerault
  • Fonction : Auteur
Jordan Dimitrov
  • Fonction : Auteur
Thomas Østerbye
  • Fonction : Auteur
Sune Justesen
  • Fonction : Auteur
Sandrine Luce
  • Fonction : Auteur
Mikhaël Attias
  • Fonction : Auteur
Bruno Kyewski
  • Fonction : Auteur
Søren Buus
  • Fonction : Auteur
F. Susan Wong
  • Fonction : Auteur
Sebastien Lacroix-Desmazes
  • Fonction : Auteur
Roberto Mallone

Résumé

The first signs of autoimmune activation leading to β-cell destruction in type 1 diabetes (T1D) appear during the first months of life. 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 PPIB15–23 T-cell receptor–transgenic 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-β 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.

Domaines

Immunologie

Dates et versions

hal-04147203 , version 1 (30-06-2023)

Identifiants

Citer

Slobodan Culina, Nimesh Gupta, Raphael Boisgard, Georgia Afonso, Marie-Claude Gagnerault, et al.. Materno-Fetal Transfer of Preproinsulin Through the Neonatal Fc Receptor Prevents Autoimmune Diabetes. Diabetes, 2015, 64 (10), pp.3532-3542. ⟨10.2337/db15-0024⟩. ⟨hal-04147203⟩

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