Plasmacytoid dendritic cells prime IL-10–producing T regulatory cells by inducible costimulator ligand

By T. Ito, Maria Yang, Yui-Hsi Wang, R. Lande, Josh Gregorio, Olivia A. Perng, X. Qin, Yong‐jun Liu, M. Gilliet. Journal of Experimental Medicine, 2007

675 citations recorded by the source corpus.

Although there is evidence for distinct roles of myeloid dendritic cells (DCs [mDCs]) and plasmacytoid pre-DCs (pDCs) in regulating T cell–mediated adaptive immunity, the concept of functional DC subsets has been questioned because of the lack of a molecular mechanism to explain these differences. In this study, we provide direct evidence that maturing mDCs and pDCs express different sets of molecules for T cell priming. Although both maturing mDCs and pDCs upregulate the expression of CD80 and CD86, only pDCs upregulate the expression of inducible costimulator ligand (ICOS-L) and maintain high expression levels upon differentiation into mature DCs. High ICOS-L expression endows maturing pDCs with the ability to induce the differentiation of naive CD4 T cells to produce interleukin-10 (IL-10) but not the T helper (Th)2 cytokines IL-4, -5, and -13. These IL-10–producing T cells are T regulatory cells, and their generation by ICOS-L is independent of pDC-driven Th1 and Th2 differentiation, although, in the later condition, some contribution from endogenous IL-4 cannot be completely ruled out. Thus, in contrast to mDCs, pDCs are poised to express ICOS-L upon maturation, which leads to the generation of IL-10–producing T regulatory cells. Our findings demonstrate that mDC and pDCs are intrinsically different in the expression of costimulatory molecules that drive distinct types of T cell responses.

Subfields: Immunology

View Paper: https://www.semanticscholar.org/paper/6303a6e8f2ad0e26f954899e9d1a708d879b21e5

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In Immunology

1. H. Hammad
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7. J. Mege
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Citations in the corpus

• The regulation of IL-10 production by immune cells (2010, background): “Signals delivered through inducible T cell co-stimulator (ICOS) have also been suggested to induce IL-10 expression by FOXP3 − regulatory T cell”
• Costimulatory molecule ICOS plays a critical role in the development of TH-17 and follicular T-helper cells by regulating c-Maf expression and IL-21 production (2008, background): “, and IL-10 is a key immunoregulatory cytokine involved in the induction of T regulatory type 1 cells, the function of Foxp3 + regulatory T cells and the suppression of autoimmunit”
• From Q Fever to Coxiella burnetii Infection: a Paradigm Change (2016, background): “within the tumoral microenvironment and tumoral growth (334, 335).”
• Plasmacytoid Dendritic Cells: Recent Progress and Open Questions (2011, background): “Thus, human pDCs induce T cell differentiation into IL-10-producing Tregs in vitro (105, 106).”
• Dendritic cells and epithelial cells: linking innate and adaptive immunity in asthma (2008, background): “Both in vitro and in vivo studies have clearly shown that pDCs can also stimulate the induction of regulatory T cells, possibly in an ICOSL-dependent manne”