title: CD69 controls the uptake of L-tryptophan through LAT1-CD98 and AhR-dependent secretion of IL-22 in psoriasis.
abstract: The 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.
authors.affiliation: Immunology Service, Hospital de la Princesa, Universidad Autónoma de Madrid, Instituto Investigación Sanitaria Princesa, Madrid, Spain.
authors.forename: Danay
authors.initials: D
authors.lastname: Cibrian
authors.affiliation: Immunology Service, Hospital de la Princesa, Universidad Autónoma de Madrid, Instituto Investigación Sanitaria Princesa, Madrid, Spain.
authors.forename: María Laura
authors.initials: ML
authors.lastname: Saiz
authors.affiliation: Immunology Service, Hospital de la Princesa, Universidad Autónoma de Madrid, Instituto Investigación Sanitaria Princesa, Madrid, Spain.
authors.forename: Hortensia
authors.initials: H
authors.lastname: de la Fuente
authors.affiliation: Department of Vascular Biology and Inflammation, Centro Nacional de Investigaciones Cardiovasculares, Madrid, Spain.
authors.forename: Raquel
authors.initials: R
authors.lastname: Sánchez-Díaz
authors.affiliation: Immunology Service, Hospital de la Princesa, Universidad Autónoma de Madrid, Instituto Investigación Sanitaria Princesa, Madrid, Spain.
authors.forename: Olga
authors.initials: O
authors.lastname: Moreno-Gonzalo
authors.affiliation: Department of Vascular Biology and Inflammation, Centro Nacional de Investigaciones Cardiovasculares, Madrid, Spain.
authors.forename: Inmaculada
authors.initials: I
authors.lastname: Jorge
authors.affiliation: Department of Vascular Biology and Inflammation, Centro Nacional de Investigaciones Cardiovasculares, Madrid, Spain.
authors.forename: Alessia
authors.initials: A
authors.lastname: Ferrarini
authors.affiliation: Department of Vascular Biology and Inflammation, Centro Nacional de Investigaciones Cardiovasculares, Madrid, Spain.
authors.forename: Jesús
authors.initials: J
authors.lastname: Vázquez
authors.affiliation: Department of Molecular Biology, Centro de Biología Molecular Severo Ochoa, Universidad Autónoma de Madrid, Madrid, Spain.
authors.forename: Carmen
authors.initials: C
authors.lastname: Punzón
authors.affiliation: Department of Molecular Biology, Centro de Biología Molecular Severo Ochoa, Universidad Autónoma de Madrid, Madrid, Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: Fresno
authors.affiliation: Immunology Service, Hospital de la Princesa, Universidad Autónoma de Madrid, Instituto Investigación Sanitaria Princesa, Madrid, Spain.
authors.forename: Miguel
authors.initials: M
authors.lastname: Vicente-Manzanares
authors.affiliation: Dermatology Service, Hospital de la Princesa, Madrid, Spain.
authors.forename: Esteban
authors.initials: E
authors.lastname: Daudén
authors.affiliation: Department of Biochemistry, Molecular Biology and Genetic, Faculty of Sciences, University of Extremadura, Badajoz, Spain.
authors.forename: Pedro M
authors.initials: PM
authors.lastname: Fernández-Salguero
authors.affiliation: Department of Vascular Biology and Inflammation, Centro Nacional de Investigaciones Cardiovasculares, Madrid, Spain.
authors.forename: Pilar
authors.identifier: 0000-0002-2392-1764
authors.initials: P
authors.lastname: Martín
authors.affiliation: Immunology Service, Hospital de la Princesa, Universidad Autónoma de Madrid, Instituto Investigación Sanitaria Princesa, Madrid, Spain.|Department of Vascular Biology and Inflammation, Centro Nacional de Investigaciones Cardiovasculares, Madrid, Spain.
authors.forename: Francisco
authors.initials: F
authors.lastname: Sánchez-Madrid
mesh_terms: D027182:Amino Acid Transport System y+ / Q000378:metabolism; D027241:Amino Acid Transport System y+L; D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D004705:Endocytosis; D027261:Fusion Regulatory Protein-1 / Q000378:metabolism; D053759:Interleukin-23 / Q000276:immunology; D007378:Interleukins / Q000378:metabolism; D037181:Lectins, C-Type / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011565:Psoriasis / Q000276:immunology*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000378:metabolism; D018336:Receptors, Aryl Hydrocarbon / Q000378:metabolism; D012867:Skin / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D058504:Th17 Cells / Q000276:immunology*; D014364:Tryptophan / Q000378:metabolism; D000097043:Interleukin-22; D000099192:CD69 Antigens
chemical_list: D027182:Amino Acid Transport System y+; D027241:Amino Acid Transport System y+L; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D027261:Fusion Regulatory Protein-1; D053759:Interleukin-23; D007378:Interleukins; D037181:Lectins, C-Type; D016692:Receptors, Antigen, T-Cell, gamma-delta; D018336:Receptors, Aryl Hydrocarbon; D014364:Tryptophan; D000097043:Interleukin-22; D000099192:CD69 Antigens; C518287:Slc7a7 protein, mouse