TYK2 and type 1 diabetes mellitus: Specific investigations using such 3D culture systems together with isogenic cellular models are needed to examine T1-IFN signaling with modulation of IFIH1 and TYK2 risk alleles as well as costimulatory pathways known to confer T1D risk (e.g., CD28/CTLA4 and CD226/TIGIT) (Table 1).