Bile retinoids imprint intestinal CD103+ dendritic cells with the ability to generate gut-tropic T cells

Abstract

Small intestinal lamina propria (SI-LP) CD103+ dendritic cells (DCs) are imprinted with an ability to metabolize vitamin A (retinol), a property underlying their enhanced capacity to induce the gut-homing receptors CC chemokine receptor-9 and α4Β7 on responding T cells. In this study, we demonstrate that imprinting of CD103+ DCs is itself critically dependent on vitamin A and occurs locally within the small intestine (SI). The major vitamin A metabolite retinoic acid (RA) induced retinol-metabolizing activity in DCs both in vitro and in vivo, suggesting a direct role for RA in this process. Consistent with this, SI-LP CD103 + DCs constitutively received RA signals in vivo at significantly higher levels than did colonic CD103+ DCs. Remarkably, SI CD103 + DCs remained imprinted in mice depleted of dietary but not of systemic retinol. We found that bile contained high levels of retinol, induced RA receptor-dependent retinol-metabolizing activity in bone marrow-derived DCs, and imprinted these cells with the ability to generate gut-tropic T cells. Taken together, these results suggest a novel and unexpected role for bile in SI-LP CD103+ DC imprinting. © 2011 Society for Mucosal Immunology.