Research output: Contribution to journal › Article › Academic › peer-review
Retinoic acid primes human dendritic cells to induce gut-homing, IL-10-producing regulatory T cells. / Bakdash, G.; Vogelpoel, L. T. C.; van Capel, T. M. M. et al.
In: Mucosal immunology, Vol. 8, No. 2, 2015, p. 265-278.Research output: Contribution to journal › Article › Academic › peer-review
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TY - JOUR
T1 - Retinoic acid primes human dendritic cells to induce gut-homing, IL-10-producing regulatory T cells
AU - Bakdash, G.
AU - Vogelpoel, L. T. C.
AU - van Capel, T. M. M.
AU - Kapsenberg, M. L.
AU - de Jong, E. C.
PY - 2015
Y1 - 2015
N2 - The vitamin A metabolite all-trans retinoic acid (RA) is an important determinant of intestinal immunity. RA primes dendritic cells (DCs) to express CD103 and produce RA themselves, which induces the gut-homing receptors α4β7 and CCR9 on T cells and amplifies transforming growth factor (TGF)-β-mediated development of Foxp3(+) regulatory T (Treg) cells. Here we investigated the effect of RA on human DCs and subsequent development of T cells. We report a novel role of RA in immune regulation by showing that RA-conditioned human DCs did not substantially enhance Foxp3 but induced α4β7(+) CCR9(+) T cells expressing high levels of interleukin (IL)-10, which were functional suppressive Treg cells. IL-10 production was dependent on DC-derived RA and was maintained when DCs were stimulated with toll-like receptor ligands. Furthermore, the presence of TGF-β during RA-DC-driven T-cell priming favored the induction of Foxp3(+) Treg cells over IL-10(+) Treg cells. Experiments with naive CD4(+) T cells stimulated by anti-CD3 and anti-CD28 antibodies in the absence of DCs emphasized that RA induces IL-10 in face of inflammatory mediators. The data thus show for the first time that RA induces IL-10-producing Treg cells and postulates a novel mechanism for IL-10 in maintaining tolerance to the intestinal microbiome
AB - The vitamin A metabolite all-trans retinoic acid (RA) is an important determinant of intestinal immunity. RA primes dendritic cells (DCs) to express CD103 and produce RA themselves, which induces the gut-homing receptors α4β7 and CCR9 on T cells and amplifies transforming growth factor (TGF)-β-mediated development of Foxp3(+) regulatory T (Treg) cells. Here we investigated the effect of RA on human DCs and subsequent development of T cells. We report a novel role of RA in immune regulation by showing that RA-conditioned human DCs did not substantially enhance Foxp3 but induced α4β7(+) CCR9(+) T cells expressing high levels of interleukin (IL)-10, which were functional suppressive Treg cells. IL-10 production was dependent on DC-derived RA and was maintained when DCs were stimulated with toll-like receptor ligands. Furthermore, the presence of TGF-β during RA-DC-driven T-cell priming favored the induction of Foxp3(+) Treg cells over IL-10(+) Treg cells. Experiments with naive CD4(+) T cells stimulated by anti-CD3 and anti-CD28 antibodies in the absence of DCs emphasized that RA induces IL-10 in face of inflammatory mediators. The data thus show for the first time that RA induces IL-10-producing Treg cells and postulates a novel mechanism for IL-10 in maintaining tolerance to the intestinal microbiome
U2 - 10.1038/mi.2014.64
DO - 10.1038/mi.2014.64
M3 - Article
C2 - 25027601
VL - 8
SP - 265
EP - 278
JO - Mucosal immunology
JF - Mucosal immunology
SN - 1933-0219
IS - 2
ER -
ID: 2438018