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Skin-draining lymph nodes contain dermis-derived CD103− dendritic cells that constitutively produce retinoic acid and induce Foxp3+ regulatory T cells

2010; Elsevier BV; Volume: 115; Issue: 10 Linguagem: Inglês

10.1182/blood-2009-09-245274

1528-0020

Martin Guilliams, Karine Crozat, Sandrine Henri, Samira Tamoutounour, Pierre Grenot, Élisabeth Devilard, Béatrice de Bovis, Lena Alexopoulou, Marc Dalod, Bernard Malissen,

Immune Cell Function and Interaction

Abstract Small intestinal CD103+ dendritic cells (DCs) have the selective ability to promote de novo generation of regulatory T cells via the production of retinoic acid (RA). Considering that aldehyde dehydrogenase (ALDH) activity controls the production of RA, we used a flow cytometry–based assay to measure ALDH activity at the single-cell level and to perform a comprehensive analysis of the RA-producing DC populations present in lymphoid and nonlymphoid mouse tissues. RA-producing DCs were primarily of the tissue-derived, migratory DC subtype and can be readily found in the skin and in the lungs as well as in their corresponding draining lymph nodes. The RA-producing skin-derived DCs were capable of triggering the generation of regulatory T cells, a finding demonstrating that the presence of RA-producing, tolerogenic DCs is not restricted to the intestinal tract as previously thought. Unexpectedly, the production of RA by skin DCs was restricted to CD103− DCs, indicating that CD103 expression does not constitute a “universal” marker for RA-producing mouse DCs. Finally, Toll-like receptor (TLR) triggering or the presence of a commensal microflora was not essential for the induction of ALDH activity in the discrete ALDH+ DC subsets that characterize tissues constituting environmental interfaces.