Cibrian, DanaySaiz, María Laurade la Fuente, HortensiaSánchez-Díaz, RaquelMoreno-Gonzalo, OlgaJorge, InmaculadaFerrarini, AlessiaVázquez, JesúsPunzón, CarmenFresno, ManuelVicente-Manzanares, MiguelDaudén, EstebanFernández-Salguero, Pedro MMartín, PilarSánchez-Madrid, Francisco2025-12-192025-12-192016-08Nat Immunol. 2016 Aug;17(8):985-96.https://hdl.handle.net/20.500.12105/27100The activation marker CD69 is expressed by skin γδ T cells. Here we found that CD69 controlled the aryl hydrocarbon receptor (AhR)-dependent secretion of interleukin 22 (IL-22) by γδ T cells, which contributed to the development of psoriasis induced by IL-23. CD69 associated with the aromatic-amino-acid-transporter complex LAT1-CD98 and regulated its surface expression and uptake of L-tryptophan (L-Trp) and the intracellular quantity of L-Trp-derived activators of AhR. In vivo administration of L-Trp, an inhibitor of AhR or IL-22 abrogated the differences between CD69-deficient mice and wild-type mice in skin inflammation. We also observed LAT1-mediated regulation of AhR activation and IL-22 secretion in circulating Vγ9(+) γδ T cells of psoriatic patients. Thus, CD69 serves as a key mediator of the pathogenesis of psoriasis by controlling LAT1-CD98-mediated metabolic cues.We thank D. Rotin (University of Toronto) for the plasmid for the expression of LAT1-mCherry; P. Taylor (University of Dundee) for antiserum to human LAT1; M. Navarro (Universidad Autónoma de Madrid, Spain) for IL-23R-GFP reporter mice; S. Bartlett for English editing; and T. Hernandez and R. Brid Doohan for technical assistance with immunohistochemistry. Supported by the Spanish Ministry of Economy and Competitiveness (SAF2011-25834 and SAF2014-55579-R to F.S.-M.; SAF2011-27330 to P.M.; and SAF2013-42850 to M.F.), Comunidad de Madrid (INDISNET-S2011/BMD-2332 to F.S.-M.; and 2010/BMD-2332 from M.F. and F.S.-M.), Instituto Salud Carlos III (Red Cardiovascular RD 12-0042-0056 to F.S.-M.; BIOIMID to M.F. and F.S.-M.), the European Research Council (ERC-2011-AdG 294340-GENTRIS to F.S.-M.) and the Ramón Areces foundation (M.F. and F.S.-M.).engVoRhttp://creativecommons.org/licenses/by-nc-nd/4.0/Attribution-NonCommercial-NoDerivatives 4.0 International2737647117(8)985-996.Nature Immunologyopen access