A functionally specialized population of mucosal CD103+ DCs induces Foxp3+ regulatory T cells via a TGF-β– and retinoic acid–dependent mechanism

JL Coombes, KRR Siddiqui… - The Journal of …, 2007 - rupress.org
JL Coombes, KRR Siddiqui, CV Arancibia-Cárcamo, J Hall, CM Sun, Y Belkaid, F Powrie
The Journal of experimental medicine, 2007rupress.org
Foxp3+ regulatory T (T reg) cells play a key role in controlling immune pathological re
actions. Many develop their regulatory activity in the thymus, but there is also evidence for
development of Foxp3+ T reg cells from naive precursors in the periphery. Recent studies
have shown that transforming growth factor (TGF)-β can promote T reg cell development in
culture, but little is known about the cellular and molecular mechanisms that mediate this
pathway under more physiological conditions. Here, we show that after antigen activation in …
Foxp3+ regulatory T (T reg) cells play a key role in controlling immune pathological re actions. Many develop their regulatory activity in the thymus, but there is also evidence for development of Foxp3+ T reg cells from naive precursors in the periphery. Recent studies have shown that transforming growth factor (TGF)-β can promote T reg cell development in culture, but little is known about the cellular and molecular mechanisms that mediate this pathway under more physiological conditions. Here, we show that after antigen activation in the intestine, naive T cells acquire expression of Foxp3. Moreover, we identify a population of CD103+ mesenteric lymph node dendritic cells (DCs) that induce the devel opment of Foxp3+ T reg cells. Importantly, promotion of T reg cell responses by CD103+ DCs is dependent on TGF-β and the dietary metabolite, retinoic acid (RA). These results newly identify RA as a cofactor in T reg cell generation, providing a mechanism via which functionally specialized gut-associated lymphoid tissue DCs can extend the repertoire of T reg cells focused on the intestine.
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