Retinoic Acid Imprints Gut-Homing Specificity on T Cells

Immunity, Vol. 21, 527–538 (2004)

Speaker：吳得嘉                       Time：14:10~15:00, May 4, 2005

Commentator：謝奇璋醫師               Place：Room 601

Abstract：

    Vitamin A is an essential precursor of tissue retinol, which participates in a variety of biological functions maintenance, such as reducing the mortality of persistent diarrhea, vision and the balance of Th1 and Th2 function. Most of the vitamin A functions depend on retinoid acid (RA), which is formed mainly through the intracellular oxidative metabolism of retinol via retinal. Above all, researchers placed an importance on the vitamin A supplementation to cure diarrhea. It was thoughtthat this function might be due to vitamin A being critical for gut immunity. Thus, Iwata, M. et al. hypothesized that vitamin A is responsible for the specific homing of T cells to the gut. First of all, the authors detected the expression of α4β7 integrin and chemokine receptor CCR9 which are able to mediate gut tropism on T cells. They found that RA treatment could enhance α4β7 integrin and CCR9 expression, suppress the skin tropism-mediated adhesion molecules as well. Furthermore, detecting by homing activities assay, the increase of these adhesion molecules could promote T cells homing to gut. In order to confirm the role of RA in the T cells homing activity, the authors fed the mice on chemically defined diet that lacked vitamin A to produce vitamin A deficient mice. Analyzing the samples from vitamin A deficient mice, they found that the α4β7+ T cells reduced in the gut and were obviously depleted from laminar propria, but not from the other organs. And also found that the dendritic cells from mesenteric lymph node and Peyer’s patches could produce vitamin A metabolizing enzymes, alcohol dehydrogenase and retinal dehydrogenase, offering RA to license T cells migration to gut tissue. In conclusion, RA plays a critical role of gut-homing specificity on T cells.

References:

1. Makoto Iwata, Asami Hirakiyama, Yuko Eshima et al.  Retinoic acid imprints gut-homing specificity on T cells. Immunity, 21, 527–538 (2004).

2. Bengt Johansson-Lindbom, William W Agace  Vitamin A helps gut T cells find their way in the dark. Nat. Med., 10, 1300-1301 (2004)