TGF-β and kynurenines as the key to infectious tolerance

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• 作者：Maria L. Belladonna ; Ciriana Orabona ; Ursula Grohmann ; Paolo Puccetti
• 刊名：Trends in Molecular Medicine
• 出版年：2009
• 出版时间：February 2009
• 年：2009
• 卷：15
• 期：2
• 页码：41-49
• 全文大小：653 K

文摘

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-β (TGF-β) 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-β actions. In these cells, autocrine, paracrine and T-cell-derived TGF-β 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-β and IDO in physiologically or therapeutically opposing human pathologies sustained by over-reacting immune responses.