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¹ Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, UK
² Mucosal Immunology Unit, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH), Bethesda, MD 20892

CORRESPONDENCE Fiona Powrie: fiona.powrie{at}path.ox.ac.uk

Foxp3⁺ regulatory T (T reg) cells play a key role in controlling immune pathological re actions. Many develop their regulatory activity in the thymus, but there is also evidence for development of Foxp3⁺ T reg cells from naive precursors in the periphery. Recent studies have shown that transforming growth factor (TGF)-ß can promote T reg cell development in culture, but little is known about the cellular and molecular mechanisms that mediate this pathway under more physiological conditions. Here, we show that after antigen activation in the intestine, naive T cells acquire expression of Foxp3. Moreover, we identify a population of CD103⁺ mesenteric lymph node dendritic cells (DCs) that induce the devel opment of Foxp3⁺ T reg cells. Importantly, promotion of T reg cell responses by CD103⁺ DCs is dependent on TGF-ß and the dietary metabolite, retinoic acid (RA). These results newly identify RA as a cofactor in T reg cell generation, providing a mechanism via which functionally specialized gut-associated lymphoid tissue DCs can extend the repertoire of T reg cells focused on the intestine.

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