In the past few years, we have been focusing on the modulation of the CD40–CD154 costimulatory interaction (Figure 1) [10,11] because of its particular effectiveness in islet transplantations [12,13] as well as its promise as a target in autoimmune diseases and related inflammatory pathologies [4,14,15], including type 1 diabetes (T1D) [16,17,18]. This evidence concerns the gene CD40LG and type 1 diabetes mellitus.