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Epigallocatechin-3 Gallate Inhibits STAT-1/JAK2/IRF-1/HLA-DR/HLA-B and Reduces CD8 MKG2D Lymphocytes of Alopecia Areata Patients

Author

Listed:
  • Fatma N. Hamed

    (Department of Infection, Immunity and Cardiovascular disease, The Medical School, University of Sheffield, Sheffield S10 2RX, UK)

  • Andrew J. G. McDonagh

    (Department of Dermatology, Royal Hallamshire Hospital, Sheffield S10 2JF, UK)

  • Sarah Almaghrabi

    (Department of Infection, Immunity and Cardiovascular disease, The Medical School, University of Sheffield, Sheffield S10 2RX, UK)

  • Youssef Bakri

    (Laboratoire de Biologie de Pathologies Humaines Faculté des Sciences, Université Mohammed V, P.B. 1014 Rabat, Morocco)

  • Andrew G. Messenger

    (Department of Dermatology, Royal Hallamshire Hospital, Sheffield S10 2JF, UK
    These authors contributed equally.)

  • Rachid Tazi-Ahnini

    (Department of Infection, Immunity and Cardiovascular disease, The Medical School, University of Sheffield, Sheffield S10 2RX, UK
    These authors contributed equally.)

Abstract

Background: Alopecia areata (AA) is associated with Interferon- γ (IFN-γ) mediated T-lymphocyte dysfunction and increased circulating Interleukine-17 (IL-17) levels. Epigallocatechin-3-gallate (EGCG) specifically inhibits IFN-γ pathways and unlike Janus Kinase 1 and 2 (JAK1/JAK2) inhibitors (tofacitinib, ruxolitinib), EGCG is safer, more cost-effective, and is a topically active agent. Our objective is to test the mode of action of EGCG in vitro and ex vivo using HaCat, Jurkat cell lines, and peripheral blood mononuclear cells (PBMCs) of AA patients and healthy controls (HCs), respectively. Methods: distribution of T helper cells (Th1, Th17), and cytotoxic cells (CD8) in PBMCs isolated from 30 AA patients and 30 HCs was investigated by flowcytomterty. In vitro treatment of HaCat and Jurkat cells with 40 μm EGCG for 48 h was performed to measure the level of phosphorylation of signal transducer and activator of transcription protein STAT1, and replicated in ex vivo model using PBMCs of AA patients. Results: Interestingly, 40 μm EGCG is capable of completely inhibiting phosphorylation of STAT1 after 48 h in HaCat and Jurkat cells and ex vivo in PBMCs of AA patients. Based on QPCR data, the action of EGCG on p-STAT1 seems to be mediated via downregulation of the expression of JAK2 but not JAK1 leading to the inhibition of human leukocyte antigens (HLA-DR and HLA-B) expression probably via IRF-1. On the other hand, AA patients have significantly increased levels of Th1, Th17, and CD8 cells and the production of IFN-γ and IL-17 by PBMCs in AA patients was significantly higher compared to HC; p = 0.008 and p = 0.006, respectively. Total numbers of CD8+ cells were not significantly different between treated and untreated samples. However, CD8+ cells with positive Natural killer group 2 member D (NKG2D) transmembrane receptor (CD8+ NKG2D+ subset) was significantly reduced when PBMCs were treated with 20 μm EGCG for 48 h. Conclusion: These results suggest that EGCG has a synergistic action that inhibits expression of HLA-DR and HLA-B molecules via the IFN-γ pathway to maintain immune privilege in HF; also it reduces CD8+ NKG2D+ subset.

Suggested Citation

  • Fatma N. Hamed & Andrew J. G. McDonagh & Sarah Almaghrabi & Youssef Bakri & Andrew G. Messenger & Rachid Tazi-Ahnini, 2018. "Epigallocatechin-3 Gallate Inhibits STAT-1/JAK2/IRF-1/HLA-DR/HLA-B and Reduces CD8 MKG2D Lymphocytes of Alopecia Areata Patients," IJERPH, MDPI, vol. 15(12), pages 1-19, December.
    • Handle: RePEc:gam:jijerp:v:15:y:2018:i:12:p:2882-:d:190900
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    References listed on IDEAS

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    1. Lynn Petukhova & Madeleine Duvic & Maria Hordinsky & David Norris & Vera Price & Yutaka Shimomura & Hyunmi Kim & Pallavi Singh & Annette Lee & Wei V. Chen & Katja C. Meyer & Ralf Paus & Colin A. B. Ja, 2010. "Genome-wide association study in alopecia areata implicates both innate and adaptive immunity," Nature, Nature, vol. 466(7302), pages 113-117, July.
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