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-B (NF-B) 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-B (IB) kinase- (IKK)-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-B activation for effector function and self-propagation. This mechanism may also underlie the protective function of glucocorticoids in pathological conditions.

Author affiliations

1. Paolo Puccetti and Ursula Grohmann are at the Department of Experimental Medicine, Section of Pharmacology, University of Perugia, Perugia 06126, Italy.

Correspondence to: Paolo Puccetti¹ Email: plopcc@tin.it