Cyp26b1 regulates the expression of the gut-homing receptor CCR9 in T cells

All-trans retinoic acid (AtRA) is an essential regulator of physiological processes and functions in lymphocyte, such as imprinting of gut-homing specificity. Concentrations of AtRA are maintained by the balance between synthesis and degradation. The cytochrome P450 family 26 (CYP26) metabolizes AtRA into inactive derivatives. We found that Cyp26b1, one of CYP26 enzymes, was expressed in CD4(+) an CD8(+) T cells in gut-related lymphoid organs. Overexpression of Cyp26b1 significantly inhibited the AtRA-induced expression of the chemokine receptor CCR9 that is required for the gut-specific homing. On the other hand, inhibiting CYP26 activity using Liarozole led to enhancement of the AtRA-induced CCR9 expression. Overall, these results suggest that gut-homing specificity of T cells can be affected by AtRA metabolism.