We are aware of the evidence that normal IL-10 signaling, nucleotide-binding oligomerization domain-containing protein 2 (NOD2)-mediated signaling and Tregs play indispensable roles in keeping normal immune homeostasis in the gastrointestinal tract by determining immunological defects in patients with IL-10 signaling deficiency, XIAP deficiency and IPEX syndrome, respectively. This evidence concerns the gene NOD2 and hyperinsulinemic hypoglycemia, familial, 4.