Format

Send to

Choose Destination
Trends Mol Med. 2009 Feb;15(2):41-9. doi: 10.1016/j.molmed.2008.11.006. Epub 2009 Jan 21.

TGF-beta and kynurenines as the key to infectious tolerance.

Author information

1
Department of Experimental Medicine, University of Perugia, Via del Giochetto, Perugia 06126, Italy.

Abstract

The maintenance of self-tolerance is an integral part of the immune surveillance process, in which cytokines act as master regulators of a complex network involving multiple cell types. On such cytokines, transforming growth factor-beta (TGF-beta) exerts a suppressive control over immune reactivity, which so far appears to be mostly confined to the T-cell compartment. Recently, dendritic cells (DCs) have been found to be both an early source and a target of TGF-beta actions. In these cells, autocrine, paracrine and T-cell-derived TGF-beta activates the tolerogenic pathway of tryptophan catabolism - mediated by indoleamine 2,3-dioxygenase (IDO) - resulting in a burst of regulatory kynurenines that contribute to establishing a state of 'infectious tolerance'. Current molecular insights suggest a synergistic potential for TGF-beta and IDO in physiologically or therapeutically opposing human pathologies sustained by over-reacting immune responses.

PMID:
19162548
DOI:
10.1016/j.molmed.2008.11.006
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center