title: CD1a on Langerhans cells controls inflammatory skin disease.
abstract: CD1a is a lipid-presenting molecule that is abundantly expressed on Langerhans cells. However, the in vivo role of CD1a has remained unclear, principally because CD1a is lacking in mice. Through the use of mice with transgenic expression of CD1a, we found that the plant-derived lipid urushiol triggered CD1a-dependent skin inflammation driven by CD4(+) helper T cells that produced the cytokines IL-17 and IL-22 (TH17 cells). Human subjects with poison-ivy dermatitis had a similar cytokine signature following CD1a-mediated recognition of urushiol. Among various urushiol congeners, we identified diunsaturated pentadecylcatechol (C15:2) as the dominant antigen for CD1a-restricted T cells. We determined the crystal structure of the CD1a-urushiol (C15:2) complex, demonstrating the molecular basis of urushiol interaction with the antigen-binding cleft of CD1a. In a mouse model and in patients with psoriasis, CD1a amplified inflammatory responses that were mediated by TH17 cells that reacted to self lipid antigens. Treatment with blocking antibodies to CD1a alleviated skin inflammation. Thus, we propose CD1a as a potential therapeutic target in inflammatory skin diseases.
authors.affiliation: Program in Cellular and Molecular Medicine, Boston Children's Hospital, Department of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Ji Hyung
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Program in Cellular and Molecular Medicine, Boston Children's Hospital, Department of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Yu
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Infection and Immunity Program &Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria, Australia.|Australian Research Council Centre of Excellence in Advanced Molecular Imaging, Monash University, Clayton, Victoria, Australia.
authors.forename: Tang
authors.initials: T
authors.lastname: Yongqing
authors.affiliation: Program in Cellular and Molecular Medicine, Boston Children's Hospital, Department of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Jessica
authors.initials: J
authors.lastname: Kim
authors.affiliation: Infection and Immunity Program &Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria, Australia.|Australian Research Council Centre of Excellence in Advanced Molecular Imaging, Monash University, Clayton, Victoria, Australia.
authors.forename: Victoria A
authors.initials: VA
authors.lastname: Hughes
authors.affiliation: Infection and Immunity Program &Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria, Australia.|Australian Research Council Centre of Excellence in Advanced Molecular Imaging, Monash University, Clayton, Victoria, Australia.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Le Nours
authors.affiliation: Infection and Immunity Program &Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria, Australia.|Australian Research Council Centre of Excellence in Advanced Molecular Imaging, Monash University, Clayton, Victoria, Australia.
authors.forename: Elsa A
authors.initials: EA
authors.lastname: Marquez
authors.affiliation: Infection and Immunity Program &Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria, Australia.
authors.forename: Anthony W
authors.initials: AW
authors.lastname: Purcell
authors.affiliation: Program in Cellular and Molecular Medicine, Boston Children's Hospital, Department of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Qi
authors.initials: Q
authors.lastname: Wan
authors.affiliation: Laboratory of Cell Regulation, Institute for Virus Research, Kyoto University, Kyoto, Japan.
authors.forename: Masahiko
authors.initials: M
authors.lastname: Sugita
authors.affiliation: Infection and Immunity Program &Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria, Australia.|Australian Research Council Centre of Excellence in Advanced Molecular Imaging, Monash University, Clayton, Victoria, Australia.|Institute of Infection and Immunity, Cardiff University, School of Medicine, Cardiff, UK.
authors.forename: Jamie
authors.initials: J
authors.lastname: Rossjohn
authors.affiliation: Program in Cellular and Molecular Medicine, Boston Children's Hospital, Department of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Florian
authors.initials: F
authors.lastname: Winau
mesh_terms: D000818:Animals; D019138:Antibodies, Blocking / Q000008:administration & dosage; D018949:Antigens, CD1 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D001324:Autoantigens / Q000378:metabolism*; D002396:Catechols / Q000737:chemistry / Q000378:metabolism*; D018360:Crystallography, X-Ray; D011040:Dermatitis, Toxicodendron / Q000276:immunology*; D004195:Disease Models, Animal; D006801:Humans; D020381:Interleukin-17 / Q000378:metabolism; D007378:Interleukins / Q000378:metabolism; D007801:Langerhans Cells / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D011487:Protein Conformation; D011565:Psoriasis / Q000276:immunology*; D058504:Th17 Cells / Q000276:immunology*; D012251:Toxicodendron / Q000276:immunology; D000097043:Interleukin-22
chemical_list: D019138:Antibodies, Blocking; D018949:Antigens, CD1; D001324:Autoantigens; D002396:Catechols; D020381:Interleukin-17; D007378:Interleukins; D000097043:Interleukin-22; C419393:CD1a antigen; C003747:urushiol