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Nature Immunology 8, 1380–1389 (1 December 2007) | doi:10.1038/ni1541

A dominant function for interleukin 27 in generating interleukin 10|[ndash]|producing anti-inflammatory T cells

Amit Awasthi , Yijun Carrier , Jean P S Peron , Estelle Bettelli , Masahito Kamanaka , Richard A Flavell , Vijay K Kuchroo , Mohamed Oukka & Howard L Weiner

Regulatory T cells (Treg cells) expressing the transcription factor Foxp3 are key in maintaining the balance of immune homeostasis. However, distinct induced T regulatory type 1 (Tr1) cells that lack Foxp3 expression also regulate T cell function, mainly by producing the immunosuppressive cytokine interleukin 10 (IL-10). However, the factors required for the induction of IL-10-producing suppressive T cells are not fully understood. Here we demonstrate that dendritic cells modified by Treg cells induced the generation of IL-10-producing Tr1 cells. The differentiation of naive CD4+ T cells into IL-10-producing cells was mediated by IL-27 produced by the Treg cell–modified dendritic cells, and transforming growth factor-β amplified the generation of induced IL-10+ Tr1 cells by IL-27. Thus, IL-27 and transforming growth factor-β promote the generation of IL-10-producing Tr1 cells.