RPTEC responded to diabetes-relevant concentrations of metabolic insults (high glucose (HG; 20 mM), methylglyoxal (MG; 10 μM), and cytokines (TNF-α, IL-6, and IL-1β)) not only by activating proinflammatory signaling molecules and increasing expression of proinflammatory cytokines but also by upregulating immunoregulatory molecules (e.g., IL-4, IL-10, TGF-β, and TSLP) and negative regulators of inflammation (e.g., IκBα, IRAK-M, Triad3A, and A20) (Fig. 6). Here, IRAK3 is linked to diabetes mellitus.