Sun Cheng-Ming, Hall Jason A, Blank Rebecca B, Bouladoux Nicolas, Oukka Mohamed, Mora J Rodrigo, Belkaid Yasmine
Mucosal Immunology Unit, Laboratory of Parasitic Diseases, National Institute for Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
J Exp Med. 2007 Aug 6;204(8):1775-85. doi: 10.1084/jem.20070602. Epub 2007 Jul 9.
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.
为维持免疫稳态，肠道免疫系统已进化出多种冗余的调节策略。在这方面，肠道是大量调节性T（Treg）细胞的家园，包括Foxp3（+）Treg细胞。因此，我们推测肠道环境优先支持胸腺外Treg细胞的发育。我们发现，口服抗原后，在淋巴细胞减少的环境中，CD4（+）T细胞向Treg细胞的外周转化主要发生在肠道相关淋巴组织（GALT）中。从小肠固有层（Lp；LpDCs）纯化的树突状细胞（DCs）相对于淋巴器官来源的DCs能促进高水平的Treg细胞转化。LpDCs这种增强的转化依赖于转化生长因子-β（TGF-β）和视黄酸（RA），RA是一种在GALT中高度表达的维生素A代谢产物。这些数据共同表明，肠道免疫系统已进化出一种自主策略来促进Treg细胞的新转化。
