Small intestine lamina propria dendritic cells promote de novo generation of Foxp3 T reg cells via retinoic acid

Journal of Experimental Medicine - Tập 204 Số 8 - Trang 1775-1785 - 2007
Cheng‐Ming Sun1, Jason A. Hall1,2, Rebecca B Blank1, Nicolas Bouladoux1, Mohamed Oukka3, J. Rodrigo Mora4, Yasmine Belkaid1
11Mucosal Immunology Unit, Laboratory of Parasitic Diseases, National Institute for Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892
22Immunology Graduate Group, University of Pennsylvania, Philadelphia, PA 19104
33Center for Neurological Diseases, Brigham Women's Hospital, Harvard's Medical School, Cambridge, MA 02139
4Gastrointestinal Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114;

Tóm tắt

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-β 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.

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Journal of Experimental Medicine

Tập 204 Số 8

1775-1785

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