TGF-beta and kynurenines as the key to infectious tolerance.
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.
Belladonna
Maria L
ML
Department of Experimental Medicine, University of Perugia, Via del Giochetto, Perugia 06126, Italy.
Orabona
Ciriana
C
Grohmann
Ursula
U
Puccetti
Paolo
P
D000818:Animals; D003713:Dendritic Cells / Q000276:immunology; D006801:Humans; D007107:Immune System / Q000502:physiology; D007108:Immune Tolerance / Q000276:immunology*; D007372:Interferons / Q000276:immunology; D007737:Kynurenine / Q000737:chemistry / Q000276:immunology*; D015398:Signal Transduction / Q000502:physiology; D013601:T-Lymphocytes / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000276:immunology*
D016212:Transforming Growth Factor beta; D007737:Kynurenine; D007372:Interferons