Going for the Gut

Abstract

Naïve circulating T cells enter peripheral lymphatic tissues throughout the body, where they may encounter antigen and become activated. The effector and memory T cells produced following activation preferentially migrate to tissues drained by the lymphatic tissue in which they were activated. For instance, T cells activated in mesenteric lymph nodes (MLN) or Peyer's Patches (PP, lymphoid tissue found in the small intestine) or activated by dendritic cells from these locations express "gut-homing receptors," such as α4β7 integrin and CCR9, and tend to migrate to the gut (see Mora and von Andrian). Noting that vitamin A reduces infant mortality associated with gastrointestinal infections, Iwata et al. showed that exposing mouse T cells to the vitamin A metabolite retinoic acid (RA) during activation stimulated expression of α4β7 integrin and CCR9 and suppressed the expression of receptors associated with homing to skin. Moreover, T cells activated in the presence of RA in vitro and then transferred into mice showed preferential homing to the small intestine compared with control T cells. Further, immunohistochemical analysis indicated that the intestinal lamina propria of vitamin A-deficient mice showed a marked reduction in T cell numbers. Dendritic cells from MLN or PP expressed enzymes associated with RA biosynthesis and synthesized RA from retinol in vitro. Pharmacological analysis indicated that the ability of these dendritic cells to stimulate α4β7 integrin expression in T cells depended on RA biosynthesis and was mediated through retinoic acid receptors. Thus, RA appears to represent a signal through which dendritic cells instruct T cells to migrate to the gut. M. Iwata, A. Hirakiyama, Y. Eshima, H. Kagechika, C. Kato, S.-Y. Song, Retinoic acid imprints gut-homing specificity on T cells. Immunity 21 , 527-538 (2004). [Online Journal] J. R. Mora, U. H. von Andrian, Retinoic acid: An educational "vitamin elixir" for gut-seeking T cells. Immunity 21 , 458-460 (2004). [Online Journal]