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

By Cheng-Ming Sun, Jason A. Hall, R. Blank, N. Bouladoux, M. Oukka, J. Mora, Y. Belkaid. Journal of Experimental Medicine, 2007

2,040 citations recorded by the source corpus.

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.

Subfields: Immunology

View Paper: https://www.semanticscholar.org/paper/da4a3f002660dc9307ecb9fe4b472c11af54205b

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Citations in the corpus

A Comprehensive Review and Update on the Pathogenesis of Inflammatory Bowel Disease (2019, background): “The GALT is believed to be the primary site where naïve conventional CD4 T cells convert to iTreg after exposure to oral antigens in a lymphogenic environment [176, 177].”
TGF-beta: a master of all T cell trades. (2008, positive): “Interestingly, administration of neutralizing TGF-β antibody or RA receptor inhibitors attenuated the generation of iTreg cells, whereas addition of RA potentiated TGF-β-induced iTreg cell differentiation (Benson et al., 2007; Coombes et al., 2007; Mucida et al., 2007; Sun et al., 2007).”
Intestinal bacterial colonization induces mutualistic regulatory T cell responses. (2011, background): “There is evidence that mucosal Treg cells are continuously generated through the action of specialized dendritic cell (DC) subsets via retinoic acid (Benson et al., 2007; Coombes et al., 2007; Iwata, 2009; Jaensson et al., 2008; Sun et al., 2007).”
Role of intestinal microbiota and metabolites on gut homeostasis and human diseases (2017, background): “Mucosal CD103+ DCs are known contributors to the conversion of Tregs depended on TGF-β and retinoic acid [80, 81].”
Immunological mechanisms of vaccination (2011, background): “For example, intestinal DCs seem programmed to induce T reg cell”
The Microbiome in Infectious Disease and Inflammation (2012, positive): “In particular, a CD103 (also known as αE-integrin)-expressing DC population in the LP preferentially promotes the generation and homing of iTreg cells to the intestinal mucosa (222, 223, 239).”
TGF-β Activation and Function in Immunity (2013, background): “CD103+ DCs in the gut are a subset of DCs proposed to contribute to intestinal tolerance by preferentially inducing naive T cells to express the transcription factor Foxp3 and become iTregs (74, 75).”
Resistance Mechanisms to Immune-Checkpoint Blockade in Cancer: Tumor-Intrinsic and -Extrinsic Factors. (2016, neutral): “…of the gut results, at least in part, from specialized populations of gut-resident APCs such as CD103+CD11b+ DCs, which can induce Treg cells through their production of the cytokine TGF-b and the vitamin A metabolite retinoic acid (Coombes et al., 2007; Mucida et al., 2007; Sun et al., 2007).”
Regulatory T cells and immune tolerance. (2008, background): “In the presence of TGF-β, retinoic acid facilitates the differentiation of naive T cells to Foxp3 + Tregs (Benson et al., 2007; Mucida et al., 2007; Sun et al., 2007; Coombes et al., 2007).”