Significant proportion of inflammatory bowel disease (IBD) patients continue to respond inconsistently to therapies, underscoring disease complexity and the need for efficacious treatment. Interleukin 21 (IL-21), which is known to support T helper (Th) cell function, is highly expressed within inflamed tissues of IBD patients compared to healthy controls. Also, inflammatory regulatory T cells (Tregs) have been linked to refractory human IBD, and the complete induction of IBD in mice has been shown to require IL-21.