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¹ Mucosal Immunology Unit, Laboratory of Parasitic Diseases, National Institute for Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892
² Immunology Graduate Group, University of Pennsylvania, Philadelphia, PA 19104
³ Center for Neurological Diseases, Brigham Women's Hospital, Harvard's Medical School, Cambridge, MA 02139
⁴ Gastrointestinal Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114

CORRESPONDENCE Yasmine Belkaid:ybelkaid{at}niaid.nih.gov

To maintain immune homeostasis, the intestinal immune system has evolved redundant regulatory strategies. In this regard, the gut is home to a large number of regulatory T (T reg) cells, including the Foxp3⁺ T reg cell. Therefore, we hypothesized that the gut environment preferentially supports extrathymic T reg cell development. We show that peripheral conversion of CD4⁺ T cells to T reg cells occurs primarily in gut-associated lymphoid tissue (GALT) after oral exposure to antigen and in a lymphopenic environment. Dendritic cells (DCs) purified from the lamina propria (Lp; LpDCs) of the small intestine were found to promote a high level of T reg cell conversion relative to lymphoid organ–derived DCs. This enhanced conversion by LpDCs was dependent on TGF-ß and retinoic acid (RA), which is a vitamin A metabolite highly expressed in GALT. Together, these data demonstrate that the intestinal immune system has evolved a self-contained strategy to promote T reg cell neoconversion.

C.-M. Sun, J. Hall, and R.B. Blank contributed equally to this paper.

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Oral tolerance: is it all retinoic acid?

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J. Exp. Med. 2007 204: 1737-1739. [Abstract] [Full Text] [PDF]

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