EDN3 and Hirschsprung disease: As the immune abnormalities were discovered in the local gut immune organs, spleen, and thymus in the murine model of Hirschsprung’s disease with either endothelin receptor B deletion or in endothelin 3-null mice, investigators suspected that endothelin 3, endothelin receptor B, or the enteric nervous system may be involved in immune regulation (Frykman et al., 2015; Gosain et al., 2015).