IDO and regulatory T cells: a role for reverse signalling and non-canonical NF-kappaB activation.
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.
Puccetti
Paolo
P
Paolo Puccetti and Ursula Grohmann are at the Department of Experimental Medicine, Section of Pharmacology, University of Perugia, Perugia 06126, Italy. plopcc@tin.it
Grohmann
Ursula
U
D000818:Animals; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D006706:Homeostasis / Q000276:immunology; D006801:Humans; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000276:immunology* / Q000378:metabolism*; D053645:Interleukin-2 Receptor alpha Subunit; D016328:NF-kappa B / Q000276:immunology*; D020239:Receptor Cross-Talk / Q000276:immunology; D015398:Signal Transduction; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D053645:Interleukin-2 Receptor alpha Subunit; D016328:NF-kappa B