Article

IDO and regulatory T cells: a role for reverse signalling and non-canonical NF-kappaB activation.

Paolo Puccetti and Ursula Grohmann are at the Department of Experimental Medicine, Section of Pharmacology, University of Perugia, Perugia 06126, Italy.
Nature Reviews Immunology 11/2007; 7(10):817-23. DOI: 10.1038/nri2163
Source: PubMed

ABSTRACT The immunoregulatory enzyme indoleamine 2,3-dioxygenase (IDO) suppresses T-cell responses and promotes immune tolerance in mammalian pregnancy, tumour resistance, chronic infection, autoimmunity and allergic inflammation. 'Reverse signalling' and 'non-canonical activation' of the transcription factor nuclear factor-kappaB (NF-kappaB) characterize the peculiar events that occur in dendritic cells when T-cell-engaged ligands work as signalling receptors and culminate in the induction of IDO expression by dendritic cells in an inhibitor of NF-kappaB (IkappaB) kinase-alpha (IKKalpha)-dependent manner. In this Opinion article, we propose that IDO acts as a bridge between dendritic cells and CD4+ regulatory T cells, and that regulatory T cells use reverse signalling and non-canonical NF-kappaB activation for effector function and self-propagation. This mechanism may also underlie the protective function of glucocorticoids in pathological conditions.

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