Indoleamine 2,3-dioxygenase 1 activation in mature cDC1 promotes tolerogenic education of inflammatory cDC2 via metabolic communication.

Autor:	Gargaro M; Department of Medicine and Surgery, University of Perugia, Perugia, Italy; Department of Pathology and Immunology, Washington University in St. Louis School of Medicine, St. Louis, MO, USA., Scalisi G; Department of Medicine and Surgery, University of Perugia, Perugia, Italy., Manni G; Department of Medicine and Surgery, University of Perugia, Perugia, Italy., Briseño CG; Department of Pathology and Immunology, Washington University in St. Louis School of Medicine, St. Louis, MO, USA., Bagadia P; Department of Pathology and Immunology, Washington University in St. Louis School of Medicine, St. Louis, MO, USA., Durai V; Department of Pathology and Immunology, Washington University in St. Louis School of Medicine, St. Louis, MO, USA., Theisen DJ; Department of Pathology and Immunology, Washington University in St. Louis School of Medicine, St. Louis, MO, USA., Kim S; Department of Pathology and Immunology, Washington University in St. Louis School of Medicine, St. Louis, MO, USA., Castelli M; Department of Medicine and Surgery, University of Perugia, Perugia, Italy., Xu CA; Department of Electrical Engineering & Computer Science, Center for Computational Biology, University of California, Berkeley, CA, USA., Meyer Zu Hörste G; Department of Neurology with Institute of Translational Neurology, University Hospital Münster, Münster, Germany., Servillo G; Department of Medicine and Surgery, University of Perugia, Perugia, Italy; University research center in functional genomics (c.u.r.ge.f.), University of Perugia, Perugia, Italy., Della Fazia MA; Department of Medicine and Surgery, University of Perugia, Perugia, Italy., Mencarelli G; Department of Medicine and Surgery, University of Perugia, Perugia, Italy., Ricciuti D; Department of Medicine and Surgery, University of Perugia, Perugia, Italy., Padiglioni E; Department of Medicine and Surgery, University of Perugia, Perugia, Italy., Giacchè N; TES Pharma, Loc. Taverne, Corciano, Italy., Colliva C; TES Pharma, Loc. Taverne, Corciano, Italy., Pellicciari R; TES Pharma, Loc. Taverne, Corciano, Italy., Calvitti M; Department of Medicine and Surgery, University of Perugia, Perugia, Italy., Zelante T; Department of Medicine and Surgery, University of Perugia, Perugia, Italy., Fuchs D; Division of Biological Chemistry, Biocenter, Innsbruck Medical University, Innsbruck, Austria., Orabona C; Department of Medicine and Surgery, University of Perugia, Perugia, Italy., Boon L; Bioceros, Utrecht, the Netherlands., Bessede A; Immusmol, Bordeaux, France., Colonna M; Department of Pathology and Immunology, Washington University in St. Louis School of Medicine, St. Louis, MO, USA., Puccetti P; Department of Medicine and Surgery, University of Perugia, Perugia, Italy; University research center in functional genomics (c.u.r.ge.f.), University of Perugia, Perugia, Italy., Murphy TL; Department of Pathology and Immunology, Washington University in St. Louis School of Medicine, St. Louis, MO, USA., Murphy KM; Department of Pathology and Immunology, Washington University in St. Louis School of Medicine, St. Louis, MO, USA; Howard Hughes Medical Institute, Washington University in St. Louis School of Medicine, St. Louis, MO, USA. Electronic address: kmurphy@wustl.edu., Fallarino F; Department of Medicine and Surgery, University of Perugia, Perugia, Italy; University research center in functional genomics (c.u.r.ge.f.), University of Perugia, Perugia, Italy. Electronic address: francesca.fallarino@unipg.it.
Jazyk:	angličtina
Zdroj:	Immunity [Immunity] 2022 Jun 14; Vol. 55 (6), pp. 1032-1050.e14.
DOI:	10.1016/j.immuni.2022.05.013
Abstrakt:	Conventional dendritic cells (cDCs), cDC1 and cDC2, act both to initiate immunity and maintain self-tolerance. The tryptophan metabolic enzyme indoleamine 2,3-dioxygenase 1 (IDO1) is used by cDCs in maintaining tolerance, but its role in different subsets remains unclear. At homeostasis, only mature CCR7 + cDC1 expressed IDO1 that was dependent on IRF8. Lipopolysaccharide treatment induced maturation and IDO1-dependent tolerogenic activity in isolated immature cDC1, but not isolated cDC2. However, both human and mouse cDC2 could induce IDO1 and acquire tolerogenic function when co-cultured with mature cDC1 through the action of cDC1-derived l-kynurenine. Accordingly, cDC1-specific inactivation of IDO1 in vivo exacerbated disease in experimental autoimmune encephalomyelitis. This study identifies a previously unrecognized metabolic communication in which IDO1-expressing cDC1 cells extend their immunoregulatory capacity to the cDC2 subset through their production of tryptophan metabolite l-kynurenine. This metabolic axis represents a potential therapeutic target in treating autoimmune demyelinating diseases. Competing Interests: Declaration of interests The authors declare no competing interests. (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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