The T box transcription factor (T-bet), which is encoded by Tbx21, plays crucial roles in the pathophysiology of experimental colitis and CD via regulation of the genetic programs of multiple lineages of immune cells such as ILC1 and Th1 cells to modulate the balance of interleukin (IL)-12- or IL-23-driven mucosal cytokine production [35,36,37]. This evidence concerns the gene TBX21 and Cowden disease.