@article{9e8a6b879ec04f1c9d10c356dd59af98,
title = "Indoleamine 2,3-dioxygenase 1 activation in mature cDC1 promotes tolerogenic education of inflammatory cDC2 via metabolic communication",
abstract = "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.",
keywords = "AhR, IDO1, IL-6, RelB, dendritic cells, immunotolerance, kynurenine, metabolites, neuroinflammation, tryptophan metabolism",
author = "Marco Gargaro and Giulia Scalisi and Giorgia Manni and Brise{\~n}o, {Carlos G.} and Prachi Bagadia and Vivek Durai and Theisen, {Derek J.} and Sunkyung Kim and Marilena Castelli and Xu, {Chenling A.} and {zu H{\"o}rste}, {Gerd Meyer} and Giuseppe Servillo and {Della Fazia}, {Maria A.} and Giulia Mencarelli and Doriana Ricciuti and Eleonora Padiglioni and Nicola Giacch{\`e} and Carolina Colliva and Roberto Pellicciari and Mario Calvitti and Teresa Zelante and Dietmar Fuchs and Ciriana Orabona and Louis Boon and Alban Bessede and Marco Colonna and Paolo Puccetti and Murphy, {Theresa L.} and Murphy, {Kenneth M.} and Francesca Fallarino",
note = "Funding Information: Supporting fundings: Italian Foundation for Cancer Research (AIRC 19903), Telethon (GGP17094), Prin 2017BZEREZ, and Italian Multiple Sclerosis Foundation (FISM 2019/R-single/012) to F.F; US National Institutes of Health (R01AI150297) to K.M.M. Conceptualization, M.G. and F.F.; investigation and methodology, M.G. G. Scalisi, C.G.B. G. Manni, P.B. V.D. T.L.M. S.K. D.J.T. T.L.M. G. Mencarelli, D.R. E.P. M. Castelli, M.A.D.F. G. Servillo, M. Calvitti, T.Z. P.P. and K.M.M.; resources, D.F. C.O. N.G. C.C. R.P. L.B. A.B. M. Colonna, and K.M.M.; formal analysis, C.A.X. and G.M.z.H.; supervision and writing—review & editing, K.M.M. and F.F. The authors declare no competing interests. Publisher Copyright: {\textcopyright} 2022 The Author(s)",
year = "2022",
month = jun,
day = "14",
doi = "10.1016/j.immuni.2022.05.013",
language = "English",
volume = "55",
pages = "1032--1050.e14",
journal = "Immunity",
issn = "1074-7613",
number = "6",
}