Figure 2.

Folate is required for the survival of mature Tregs. Once naïve T cells differentiate into Tregs, they highly express folate receptor 4 (FR4), which regulates the development and function of Tregs. The binding of folate to FR4 stimulates the production of the anti-apoptotic molecules Bcl-2 and bcl-xL, allowing for the survival of functional Tregs. Folate deficiency affects the survival of Tregs, leading to a reduction Bcl-2 and Bcl-xL and hence, an increase in Treg apoptosis. Impaired Treg function may impair immunosuppression and lead to increased susceptibility to intestinal inflammation.