Cutting Edge: Autocrine TGF-β Sustains Default Tolerogenesis by IDO-Competent Dendritic Cells | Zendy

Maria Laura Belladonna | Zendy; Claudia Volpi | Zendy; Roberta Bianchi | Zendy; Carmine Vacca | Zendy; Ciriana Orabona | Zendy; Maria Teresa Pallotta | Zendy; Louis Boon | Zendy; Stefania Gizzi | Zendy; Maria C. Fioretti | Zendy; Ursula Grohmann | Zendy; Paolo Puccetti | Zendy

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Cutting Edge: Autocrine TGF-β Sustains Default Tolerogenesis by IDO-Competent Dendritic Cells

Author(s) -

Maria Laura Belladonna,

Claudia Volpi,

Roberta Bianchi,

Carmine Vacca,

Ciriana Orabona,

Maria Teresa Pallotta,

Louis Boon,

Stefania Gizzi,

Maria C. Fioretti,

Ursula Grohmann,

Paolo Puccetti

Publication year - 2008

Publication title -

the journal of immunology

Language(s) - Uncategorized

Resource type - Journals

SCImago Journal Rank - 2.737

H-Index - 372

eISSN - 1550-6606

pISSN - 0022-1767

DOI - 10.4049/jimmunol.181.8.5194

Subject(s) - autocrine signalling , cd8 , cytotoxic t cell , microbiology and biotechnology , immunology , tgf beta signaling pathway , immune tolerance , phenotype , biology , transforming growth factor , immune system , receptor , gene , in vitro , genetics

CD8(-) and CD8(+) dendritic cells (DCs) are distinct subsets of mouse splenic accessory cells with opposite but flexible programs of Ag presentation, leading to immunogenic and tolerogenic responses, respectively. In this study, we show that the default tolerogenic function of CD8(+) DCs relies on autocrine TGF-beta, which sustains the activation of IDO in response to environmental stimuli. CD8(-) DCs do not produce TGF-beta, yet externally added TGF-beta induces IDO and turns those cells from immunogenic into tolerogenic cells. The acquisition of a suppressive phenotype by CD8(-) DCs correlates with activation of the PI3K/Akt and noncanonical NF-kappaB pathways. These data are the first to link TGF-beta signaling with IDO in controlling spontaneous tolerogenesis by DCs.

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