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

P Puccetti, U Grohmann - Nature Reviews Immunology, 2007 - nature.com
Nature Reviews Immunology, 2007nature.com
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-κB (NF-κB)
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 …
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-κB (NF-κB) 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-κB (IκB) kinase-α (IKKα)-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-κB activation for effector function and self-propagation. This mechanism may also underlie the protective function of glucocorticoids in pathological conditions.
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