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Blood, 15 December 2006, Vol. 108, No. 13, pp. 4118-4125. Prepublished online as a Blood First Edition Paper on August 10, 2006; DOI 10.1182/blood-2006-03-006700. This Article Full Text (PDF) All Versions of this Article: blood-2006-03-006700v1 108/13/4118    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Della Chiesa, M. Articles by Vitale, M. Search for Related Content PubMed PubMed Citation Articles by Della Chiesa, M. Articles by Vitale, M. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted March 2, 2006 Accepted July 25, 2006 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*, and Massimo Vitale DI.ME.S. Dipartimento di Medicina Sperimentale Universita di Genova, Genova, Italy IST - Istituto Nazionale per la Ricerca sul Cancro - Genova, Italy Istituto G. Gaslini - Genova-Quarto, Italy Istituto G. Gaslini - Genova, Italy IST - Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy * Corresponding author; email: alemoret{at}unige.it. 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 demonstrate that also 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 (DC), that are mainly recognized via the NKp30 receptor. The effect of L-kynurenine, which is effective both at the transcriptional and at the protein level, can be reverted, since NK cells were found to recover their functional competence after washing. 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Spaggiari, A. Capobianco, H. Abdelrazik, F. Becchetti, M. C. Mingari, and L. Moretta Mesenchymal stem cells inhibit natural killer-cell proliferation, cytotoxicity, and cytokine production: role of indoleamine 2,3-dioxygenase and prostaglandin E2 Blood, February 1, 2008; 111(3): 1327 - 1333. [Abstract] [Full Text] [PDF] J. Li, A. Meinhardt, M.-E. Roehrich, D. Golshayan, J. Dudler, M. Pagnotta, M. Trucco, and G. Vassalli Indoleamine 2,3-dioxygenase gene transfer prolongs cardiac allograft survival Am J Physiol Heart Circ Physiol, December 1, 2007; 293(6): H3415 - H3423. [Abstract] [Full Text] [PDF]

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