title: Programmed cell death ligand 1 alleviates psoriatic inflammation by suppressing IL-17A production from programmed cell death 1-high T cells.
abstract: Psoriasis is one of the most common chronic inflammatory diseases of the skin. Recently, IL-17-producing T cells have been shown to play a critical role in psoriatic inflammation. Programmed cell death 1 (PD-1) is a coinhibitory receptor expressed on T cells in various chronic inflammatory diseases; however, the expression and function of PD-1 during psoriatic inflammation have not previously been characterized.
  
  
  
  We examined PD-1 expression on IL-17A-producing T cells from imiquimod-treated mice and patients with psoriasis. Additionally, we investigated the therapeutic effect of recombinant programmed cell death ligand 1 (PD-L1) protein on imiquimod-induced psoriatic inflammation.
  
  
  
  PD-1 expression on IL-17A-producing γδ T cells from imiquimod-treated mice was examined by means of multicolor flow cytometric analysis. In the psoriatic skin of patients, PD-1 and IL-17A expression was analyzed by using immunofluorescence. The therapeutic effect of PD-L1-Fc fusion protein (PD-L1-Fc) was assessed in imiquimod-treated mice ex vivo and in vivo.
  
  
  
  During imiquimod-induced psoriatic inflammation, PD-1 is overexpressed on CD27(-)Vγ1(-) γδ T cells. Furthermore, PD-1 expression on IL-17A(+) T cells was confirmed in psoriatic skin tissues from patients and imiquimod-treated mice. In the CD27(-)Vγ1(-) γδ T-cell population, Vγ4(-) γδ T cells with Vγ6 mRNA expression showed a high level of PD-1 expression. Furthermore, these PD-1(hi)Vγ4(-) (Vγ6(+)) γδ T cells were specialized for anti-CD3-induced IL-17A production, which was inhibited by PD-L1-Fc treatment. In imiquimod-treated mice PD-L1-Fc reduced psoriatic inflammation when given alone and enhanced the therapeutic effect of anti-p40 when given in combination.
  
  
  
  PD-1 is overexpressed in IL-17A-producing T cells in both imiquimod-treated mice and patients with psoriasis. Moreover, recombinant PD-L1-Fc alleviates psoriatic inflammation in imiquimod-treated mice.
authors.affiliation: Laboratory of Immunology and Infectious Diseases, Graduate School of Medical Science and Engineering, KAIST, Daejeon, Korea; Department of Dermatology and Cutaneous Biology Research Institute, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Jong Hoon
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Laboratory of Immunology and Infectious Diseases, Graduate School of Medical Science and Engineering, KAIST, Daejeon, Korea.
authors.forename: Young Joon
authors.initials: YJ
authors.lastname: Choi
authors.affiliation: Genexine, Seongnam, Korea.
authors.forename: Byung Ha
authors.initials: BH
authors.lastname: Lee
authors.affiliation: Division of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology, Pohang, Korea.
authors.forename: Mi-Young
authors.initials: MY
authors.lastname: Song
authors.affiliation: Laboratory of Immunology and Infectious Diseases, Graduate School of Medical Science and Engineering, KAIST, Daejeon, Korea.
authors.forename: Chae Yeon
authors.initials: CY
authors.lastname: Ban
authors.affiliation: Laboratory of Immunology and Infectious Diseases, Graduate School of Medical Science and Engineering, KAIST, Daejeon, Korea.
authors.forename: Jihye
authors.initials: J
authors.lastname: Kim
authors.affiliation: Laboratory of Immunology and Infectious Diseases, Graduate School of Medical Science and Engineering, KAIST, Daejeon, Korea.
authors.forename: Junsik
authors.initials: J
authors.lastname: Park
authors.affiliation: Department of Dermatology and Cutaneous Biology Research Institute, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Song-Ee
authors.initials: SE
authors.lastname: Kim
authors.affiliation: Department of Environmental Medical Biology, Institute of Tropical Medicine, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Tae-Gyun
authors.initials: TG
authors.lastname: Kim
authors.affiliation: Laboratory of Translational Immunology and Vaccinology, Graduate School of Medical Science and Engineering, KAIST, Daejeon, Korea.
authors.forename: Su-Hyung
authors.initials: SH
authors.lastname: Park
authors.affiliation: Department of Environmental Medical Biology, Institute of Tropical Medicine, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Hyoung-Pyo
authors.initials: HP
authors.lastname: Kim
authors.affiliation: Genexine, Seongnam, Korea; Division of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology, Pohang, Korea.
authors.forename: Young-Chul
authors.initials: YC
authors.lastname: Sung
authors.affiliation: Department of Dermatology and Cutaneous Biology Research Institute, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea. Electronic address: kimsc@yuhs.ac.
authors.forename: Soo-Chan
authors.initials: SC
authors.lastname: Kim
authors.affiliation: Laboratory of Immunology and Infectious Diseases, Graduate School of Medical Science and Engineering, KAIST, Daejeon, Korea. Electronic address: ecshin@kaist.ac.kr.
authors.forename: Eui-Cheol
authors.initials: EC
authors.lastname: Shin
mesh_terms: D000276:Adjuvants, Immunologic; D000634:Aminoquinolines; D000818:Animals; D060890:B7-H1 Antigen / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D000077271:Imiquimod; D007249:Inflammation / Q000378:metabolism; D020381:Interleukin-17 / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D061026:Programmed Cell Death 1 Receptor / Q000378:metabolism*; D011565:Psoriasis / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism*; D011994:Recombinant Proteins / Q000494:pharmacology / Q000627:therapeutic use; D012867:Skin / Q000187:drug effects / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000378:metabolism*
chemical_list: D000276:Adjuvants, Immunologic; D000634:Aminoquinolines; D060890:B7-H1 Antigen; C508717:IL17A protein, human; D020381:Interleukin-17; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; D011994:Recombinant Proteins; D000077271:Imiquimod
keywords: IL-17A; Psoriasis; T cell; programmed cell death 1; programmed cell death ligand 1