Jong Hoon Kim1, Young Joon Choi2, Byung Ha Lee3, Mi-Young Song4, Chae Yeon Ban2, Jihye Kim2, Junsik Park2, Song-Ee Kim5, Tae-Gyun Kim6, Su-Hyung Park7, Hyoung-Pyo Kim6, Young-Chul Sung8, Soo-Chan Kim9, Eui-Cheol Shin10. 1. 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. 2. Laboratory of Immunology and Infectious Diseases, Graduate School of Medical Science and Engineering, KAIST, Daejeon, Korea. 3. Genexine, Seongnam, Korea. 4. Division of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology, Pohang, Korea. 5. Department of Dermatology and Cutaneous Biology Research Institute, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea. 6. Department of Environmental Medical Biology, Institute of Tropical Medicine, Yonsei University College of Medicine, Seoul, Korea. 7. Laboratory of Translational Immunology and Vaccinology, Graduate School of Medical Science and Engineering, KAIST, Daejeon, Korea. 8. Genexine, Seongnam, Korea; Division of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology, Pohang, Korea. 9. Department of Dermatology and Cutaneous Biology Research Institute, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea. Electronic address: kimsc@yuhs.ac. 10. Laboratory of Immunology and Infectious Diseases, Graduate School of Medical Science and Engineering, KAIST, Daejeon, Korea. Electronic address: ecshin@kaist.ac.kr.
Abstract
BACKGROUND: 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. OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.
BACKGROUND: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. OBJECTIVE: 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. METHODS: 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. RESULTS: 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 micePD-L1-Fc reduced psoriatic inflammation when given alone and enhanced the therapeutic effect of anti-p40 when given in combination. CONCLUSION: 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: Alessandra Petrelli; Gerdien Mijnheer; David P Hoytema van Konijnenburg; Maria M van der Wal; Barbara Giovannone; Enric Mocholi; Nadia Vazirpanah; Jasper C Broen; Dirkjan Hijnen; Bas Oldenburg; Paul J Coffer; Sebastian J Vastert; Berent J Prakken; Eric Spierings; Aridaman Pandit; Michal Mokry; Femke van Wijk Journal: J Clin Invest Date: 2018-08-02 Impact factor: 14.808
Authors: Ji Hye Jeong; Su Jin Choi; Soo Min Ahn; Ji Seon Oh; Yong-Gil Kim; Chang-Keun Lee; Bin Yoo; Seokchan Hong Journal: Arthritis Res Ther Date: 2021-03-19 Impact factor: 5.156
Authors: Jenna L Collier; Sarah A Weiss; Kristen E Pauken; Debattama R Sen; Arlene H Sharpe Journal: Nat Immunol Date: 2021-06-17 Impact factor: 31.250
Authors: Sigrun R Hofmann; Emil Carlsson; Franz Kapplusch; Ana L Carvalho; Triantafillos Liloglou; Felix Schulze; Susanne Abraham; Sarah Northey; Susanne Russ; Anna E A Surace; Nobuya Yoshida; George C Tsokos; Christian M Hedrich Journal: J Immunol Date: 2021-06-16 Impact factor: 5.422