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


ABSTRACT: 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-beta 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.

SUBMITTER: Sun CM 

PROVIDER: S-EPMC2118682 | biostudies-literature | 2007 Aug

REPOSITORIES: biostudies-literature

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

Sun Cheng-Ming CM   Hall Jason A JA   Blank Rebecca B RB   Bouladoux Nicolas N   Oukka Mohamed M   Mora J Rodrigo JR   Belkaid Yasmine Y  

The Journal of experimental medicine 20070709 8


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  ...[more]

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