The tryptophan catabolite L-kynurenine inhibits the surface expression of NKp46- and NKG2D-activating receptors and regulates NK-cell function

Mariella Della Chiesa, Simona Carlomagno, Guido Frumento, Mirna Balsamo, Claudia Cantoni, Romana Conte, Lorenzo Moretta, Alessandro Moretta, Massimo Vitale

Research output: Contribution to journalArticlepeer-review

Abstract

Tryptophan (Trp) catabolism mediated by indoleamine 2,3-dioxygenase (IDO) plays a central role in the regulation of T-cell-mediated immune responses. In this study, we also demonstrate that natural killer (NK)-cell function can be influenced by IDO. Indeed, L-kynurenine, a Trp-derived catabolite resulting from IDO activity, was found to prevent the cytokine-mediated up-regulation of the expression and function of specific triggering receptors responsible for the induction of NK-cell-mediated killing. The effect of L-kynurenine appears to be restricted to NKp46 and NKG2D, while it does not affect other surface receptors such as NKp30 or CD16. As a consequence, L-kynurenine-treated NK cells display impaired ability to kill target cells recognized via NKp46 and NKG2D. Instead, they maintain the ability to kill targets, such as dendritic cells (DCs), that are mainly recognized via the NKp30 receptor. The effect of L-kynurenine, which is effective at both the transcriptional and the protein level, can be reverted, since NK cells were found to recover their functional competence after washing.

Original languageEnglish
Pages (from-to)4118-4125
Number of pages8
JournalBlood
Volume108
Issue number13
DOIs
Publication statusPublished - Dec 15 2006

ASJC Scopus subject areas

  • Hematology

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