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819 results on '"Sawada, Yu"'

1. Cutaneous innate immune tolerance is mediated by epigenetic control of MAP2K3 by HDAC8/9

Author

Sawada, Yu, Nakatsuji, Teruaki, Dokoshi, Tatsuya, Kulkarni, Nikhil Nitin, Liggins, Marc C, Sen, George, and Gallo, Richard L

Subjects
Biomedical and Clinical Sciences, Immunology, Prevention, Infectious Diseases, Genetics, Emerging Infectious Diseases, Biodefense, Clinical Research, Vaccine Related, Underpinning research, 1.1 Normal biological development and functioning, Skin, Inflammatory and immune system, Animals, Cells, Cultured, Dendritic Cells, Epigenesis, Genetic, Histone Deacetylases, Humans, Imiquimod, Immune Tolerance, Immunity, Innate, Keratinocytes, MAP Kinase Kinase 3, Mice, Transgenic, Repressor Proteins, Staphylococcus aureus, T-Lymphocytes, Toll-Like Receptors, Ultraviolet Rays, Clinical sciences
Abstract

The skin typically tolerates exposure to various microbes and chemicals in the environment. Here, we investigated how the epidermis maintains this innate immune tolerance to stimuli that are recognized by Toll-like receptors (TLRs). Loss of tolerance to TLR ligands occurred after silencing of the histone deacetylases (HDACs) HDAC8 and HDAC9 in keratinocytes. Transcriptional analysis identified MAP2K3 as suppressed by HDAC8/9 activity and a potential key intermediary for establishing this tolerance. HDAC8/9 influenced acetylation at H3K9 and H3K27 marks in the MAP2K3 promoter. Proteomic analysis further identified SSRP1 and SUPT16H as associated with HDAC8/9 and responsible for transcriptional elongation of MAP2K3. Silencing of MAP2K3 blocked the capacity of HDAC8/9 to influence cytokine responses. Relevance in vivo was supported by observations of increased MAP2K3 in human inflammatory skin conditions and the capacity of keratinocyte HDAC8/9 to influence dendritic cell maturation and T cell proliferation. Keratinocyte-specific deletion of HDAC8/9 also increased inflammation in mice after exposure to ultraviolet radiation, imiquimod, or Staphylococcus aureus These findings define a mechanism for the epidermis to regulate inflammation in the presence of ubiquitous TLR ligands.

Published
2021

2. Role of Epigenetics in the Regulation of Immune Functions of the Skin

Author

Sawada, Yu and Gallo, Richard L

Subjects
Biomedical and Clinical Sciences, Immunology, Genetics, Underpinning research, 1.1 Normal biological development and functioning, Aetiology, 2.1 Biological and endogenous factors, Inflammatory and immune system, Skin, Dermatitis, Epigenesis, Genetic, Histones, Humans, Macrophages, T-Lymphocytes, Clinical Sciences, Oncology and Carcinogenesis, Dermatology & Venereal Diseases, Clinical sciences
Abstract

This review is intended to illuminate the emerging understanding of epigenetic modifications that regulate both adaptive and innate immunity in the skin. Host defense of the epidermis and dermis involves the interplay of many cell types to enable homeostasis; tolerance to the external environment; and appropriate response to transient microbial, chemical, and physical insults. To understand this process, the study of cutaneous immunology has focused on immune responses that reflect both adaptive learned and genetically programmed innate defense systems. However, recent advances have begun to reveal that epigenetic modifications of chromatin structure also have a major influence on the skin immune system. This deeper understanding of how enzymatic changes in chromatin structure can modify the skin immune system and may explain how environmental exposures during life, and the microbiome, lead to both short-term and long-term changes in cutaneous allergic and other inflammatory processes. Understanding the mechanisms responsible for alterations in gene and chromatin structure within skin immunocytes could provide key insights into the pathogenesis of inflammatory skin diseases that have thus far evaded understanding by dermatologists.

Published
2021

44. Supplementary Figure 2 from Phase I Trial of a Glypican-3–Derived Peptide Vaccine for Advanced Hepatocellular Carcinoma: Immunologic Evidence and Potential for Improving Overall Survival

Author

Sawada, Yu, primary, Yoshikawa, Toshiaki, primary, Nobuoka, Daisuke, primary, Shirakawa, Hirofumi, primary, Kuronuma, Toshimitsu, primary, Motomura, Yutaka, primary, Mizuno, Shoichi, primary, Ishii, Hiroshi, primary, Nakachi, Kohei, primary, Konishi, Masaru, primary, Nakagohri, Toshio, primary, Takahashi, Shinichiro, primary, Gotohda, Naoto, primary, Takayama, Tadatoshi, primary, Yamao, Kenji, primary, Uesaka, Katsuhiko, primary, Furuse, Junji, primary, Kinoshita, Taira, primary, and Nakatsura, Tetsuya, primary

Published
2023
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45. Supplementary Figure 1 from Phase I Trial of a Glypican-3–Derived Peptide Vaccine for Advanced Hepatocellular Carcinoma: Immunologic Evidence and Potential for Improving Overall Survival

Author

Sawada, Yu, primary, Yoshikawa, Toshiaki, primary, Nobuoka, Daisuke, primary, Shirakawa, Hirofumi, primary, Kuronuma, Toshimitsu, primary, Motomura, Yutaka, primary, Mizuno, Shoichi, primary, Ishii, Hiroshi, primary, Nakachi, Kohei, primary, Konishi, Masaru, primary, Nakagohri, Toshio, primary, Takahashi, Shinichiro, primary, Gotohda, Naoto, primary, Takayama, Tadatoshi, primary, Yamao, Kenji, primary, Uesaka, Katsuhiko, primary, Furuse, Junji, primary, Kinoshita, Taira, primary, and Nakatsura, Tetsuya, primary

Published
2023
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46. Supplementary Figure Legend from Phase I Trial of a Glypican-3–Derived Peptide Vaccine for Advanced Hepatocellular Carcinoma: Immunologic Evidence and Potential for Improving Overall Survival

Author

Sawada, Yu, primary, Yoshikawa, Toshiaki, primary, Nobuoka, Daisuke, primary, Shirakawa, Hirofumi, primary, Kuronuma, Toshimitsu, primary, Motomura, Yutaka, primary, Mizuno, Shoichi, primary, Ishii, Hiroshi, primary, Nakachi, Kohei, primary, Konishi, Masaru, primary, Nakagohri, Toshio, primary, Takahashi, Shinichiro, primary, Gotohda, Naoto, primary, Takayama, Tadatoshi, primary, Yamao, Kenji, primary, Uesaka, Katsuhiko, primary, Furuse, Junji, primary, Kinoshita, Taira, primary, and Nakatsura, Tetsuya, primary

Published
2023
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48. Supplementary Table 2 from Phase I Trial of a Glypican-3–Derived Peptide Vaccine for Advanced Hepatocellular Carcinoma: Immunologic Evidence and Potential for Improving Overall Survival

Author

Sawada, Yu, primary, Yoshikawa, Toshiaki, primary, Nobuoka, Daisuke, primary, Shirakawa, Hirofumi, primary, Kuronuma, Toshimitsu, primary, Motomura, Yutaka, primary, Mizuno, Shoichi, primary, Ishii, Hiroshi, primary, Nakachi, Kohei, primary, Konishi, Masaru, primary, Nakagohri, Toshio, primary, Takahashi, Shinichiro, primary, Gotohda, Naoto, primary, Takayama, Tadatoshi, primary, Yamao, Kenji, primary, Uesaka, Katsuhiko, primary, Furuse, Junji, primary, Kinoshita, Taira, primary, and Nakatsura, Tetsuya, primary

Published
2023
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49. Supplementary Table 1 from Phase I Trial of a Glypican-3–Derived Peptide Vaccine for Advanced Hepatocellular Carcinoma: Immunologic Evidence and Potential for Improving Overall Survival

Author

Sawada, Yu, primary, Yoshikawa, Toshiaki, primary, Nobuoka, Daisuke, primary, Shirakawa, Hirofumi, primary, Kuronuma, Toshimitsu, primary, Motomura, Yutaka, primary, Mizuno, Shoichi, primary, Ishii, Hiroshi, primary, Nakachi, Kohei, primary, Konishi, Masaru, primary, Nakagohri, Toshio, primary, Takahashi, Shinichiro, primary, Gotohda, Naoto, primary, Takayama, Tadatoshi, primary, Yamao, Kenji, primary, Uesaka, Katsuhiko, primary, Furuse, Junji, primary, Kinoshita, Taira, primary, and Nakatsura, Tetsuya, primary

Published
2023
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