TGFβ and Retinoic Acid Intersect in Immune-Regulation

Transforming growth factor (TGF beta) prevents T(H)1 and T(H)2 differentiation and converts naive CD4 cells into Foxp3-expressing T regulatory (Treg) cell.(1,2) In sharp contrast, in the presence of pro-inflammatory cytokines, including IL-6, TGF beta not only inhibits Foxp3 expression but also promotes the differentiation of pro-inflammatory IL17-producing CD4 effector T (T(H)17) cells.(3-5) This reciprocal TGF beta-dependent differentiation imposes a critical dilemma between pro- and anti-inflammatory immunity and suggests that a sensitive regulatory mechanism must exist to control TGF beta-driven T(H)17 effector and Treg differentiation. A vitamin A metabolite, retinoic acid (RA), was recently identified as a key modulator of TGF beta-driven-immune deviation capable of suppressing T(H)17 differentiation while promoting Foxp3(+) Treg generation.(6-10)