Frontiers in Immunology (Jan 2021)
Zdhhc2 Is Essential for Plasmacytoid Dendritic Cells Mediated Inflammatory Response in Psoriasis
- Binhui Zhou,
- Binhui Zhou,
- Wenyi Yang,
- Wenyi Yang,
- Wushan Li,
- Wushan Li,
- Le He,
- Le He,
- Liaoxun Lu,
- Liaoxun Lu,
- Liaoxun Lu,
- Lichen Zhang,
- Lichen Zhang,
- Zhuangzhuang Liu,
- Zhuangzhuang Liu,
- Ying Wang,
- Tianzhu Chao,
- Tianzhu Chao,
- Rong Huang,
- Rong Huang,
- Yanrong Gu,
- Yanrong Gu,
- Tingting Jia,
- Tingting Jia,
- Qiaoli Liu,
- Qiaoli Liu,
- Shuanghua Tian,
- Shuanghua Tian,
- Philippe Pierre,
- Philippe Pierre,
- Philippe Pierre,
- Takahiro Maeda,
- Yinming Liang,
- Yinming Liang,
- Yinming Liang,
- Eryan Kong
Affiliations
- Binhui Zhou
- Laboratory of Mouse Genetics, Institute of Psychiatry and Neuroscience, Xinxiang Medical University, Henan, China
- Binhui Zhou
- Laboratory of Genetic Regulators in the Immune System, Henan Collaborative Innovation Center of Molecular Diagnosis and Laboratory Medicine, Xinxiang Medical University, Henan, China
- Wenyi Yang
- Laboratory of Genetic Regulators in the Immune System, Henan Collaborative Innovation Center of Molecular Diagnosis and Laboratory Medicine, Xinxiang Medical University, Henan, China
- Wenyi Yang
- Henan Key Laboratory of Immunology and Targeted Therapy, School of Laboratory Medicine, Xinxiang Medical University, Henan, China
- Wushan Li
- Laboratory of Mouse Genetics, Institute of Psychiatry and Neuroscience, Xinxiang Medical University, Henan, China
- Wushan Li
- Laboratory of Genetic Regulators in the Immune System, Henan Collaborative Innovation Center of Molecular Diagnosis and Laboratory Medicine, Xinxiang Medical University, Henan, China
- Le He
- Laboratory of Genetic Regulators in the Immune System, Henan Collaborative Innovation Center of Molecular Diagnosis and Laboratory Medicine, Xinxiang Medical University, Henan, China
- Le He
- Henan Key Laboratory of Immunology and Targeted Therapy, School of Laboratory Medicine, Xinxiang Medical University, Henan, China
- Liaoxun Lu
- Laboratory of Mouse Genetics, Institute of Psychiatry and Neuroscience, Xinxiang Medical University, Henan, China
- Liaoxun Lu
- Laboratory of Genetic Regulators in the Immune System, Henan Collaborative Innovation Center of Molecular Diagnosis and Laboratory Medicine, Xinxiang Medical University, Henan, China
- Liaoxun Lu
- Henan Key Laboratory of Immunology and Targeted Therapy, School of Laboratory Medicine, Xinxiang Medical University, Henan, China
- Lichen Zhang
- Laboratory of Genetic Regulators in the Immune System, Henan Collaborative Innovation Center of Molecular Diagnosis and Laboratory Medicine, Xinxiang Medical University, Henan, China
- Lichen Zhang
- Henan Key Laboratory of Immunology and Targeted Therapy, School of Laboratory Medicine, Xinxiang Medical University, Henan, China
- Zhuangzhuang Liu
- Laboratory of Mouse Genetics, Institute of Psychiatry and Neuroscience, Xinxiang Medical University, Henan, China
- Zhuangzhuang Liu
- Laboratory of Genetic Regulators in the Immune System, Henan Collaborative Innovation Center of Molecular Diagnosis and Laboratory Medicine, Xinxiang Medical University, Henan, China
- Ying Wang
- Laboratory of Mouse Genetics, Institute of Psychiatry and Neuroscience, Xinxiang Medical University, Henan, China
- Tianzhu Chao
- Laboratory of Mouse Genetics, Institute of Psychiatry and Neuroscience, Xinxiang Medical University, Henan, China
- Tianzhu Chao
- Laboratory of Genetic Regulators in the Immune System, Henan Collaborative Innovation Center of Molecular Diagnosis and Laboratory Medicine, Xinxiang Medical University, Henan, China
- Rong Huang
- Laboratory of Genetic Regulators in the Immune System, Henan Collaborative Innovation Center of Molecular Diagnosis and Laboratory Medicine, Xinxiang Medical University, Henan, China
- Rong Huang
- Henan Key Laboratory of Immunology and Targeted Therapy, School of Laboratory Medicine, Xinxiang Medical University, Henan, China
- Yanrong Gu
- Laboratory of Genetic Regulators in the Immune System, Henan Collaborative Innovation Center of Molecular Diagnosis and Laboratory Medicine, Xinxiang Medical University, Henan, China
- Yanrong Gu
- Henan Key Laboratory of Immunology and Targeted Therapy, School of Laboratory Medicine, Xinxiang Medical University, Henan, China
- Tingting Jia
- Laboratory of Genetic Regulators in the Immune System, Henan Collaborative Innovation Center of Molecular Diagnosis and Laboratory Medicine, Xinxiang Medical University, Henan, China
- Tingting Jia
- Henan Key Laboratory of Immunology and Targeted Therapy, School of Laboratory Medicine, Xinxiang Medical University, Henan, China
- Qiaoli Liu
- Laboratory of Genetic Regulators in the Immune System, Henan Collaborative Innovation Center of Molecular Diagnosis and Laboratory Medicine, Xinxiang Medical University, Henan, China
- Qiaoli Liu
- Henan Key Laboratory of Immunology and Targeted Therapy, School of Laboratory Medicine, Xinxiang Medical University, Henan, China
- Shuanghua Tian
- Laboratory of Genetic Regulators in the Immune System, Henan Collaborative Innovation Center of Molecular Diagnosis and Laboratory Medicine, Xinxiang Medical University, Henan, China
- Shuanghua Tian
- Henan Key Laboratory of Immunology and Targeted Therapy, School of Laboratory Medicine, Xinxiang Medical University, Henan, China
- Philippe Pierre
- Centre d’Immunologie de Marseille-Luminy (CIML), INSERM, CNRS, Aix Marseille Université, Marseille, France
- Philippe Pierre
- Department of Medical Sciences, Institute for Research in Biomedicine (iBiMED) and Ilidio Pinho Foundation, University of Aveiro, Aveiro, Portugal
- Philippe Pierre
- Department of Microbiology and Immunology, Shanghai Institute of Immunology, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Takahiro Maeda
- Department of Island and Community Medicine, Island Medical Research Institute, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
- Yinming Liang
- Laboratory of Mouse Genetics, Institute of Psychiatry and Neuroscience, Xinxiang Medical University, Henan, China
- Yinming Liang
- Laboratory of Genetic Regulators in the Immune System, Henan Collaborative Innovation Center of Molecular Diagnosis and Laboratory Medicine, Xinxiang Medical University, Henan, China
- Yinming Liang
- Henan Key Laboratory of Immunology and Targeted Therapy, School of Laboratory Medicine, Xinxiang Medical University, Henan, China
- Eryan Kong
- Laboratory of Mouse Genetics, Institute of Psychiatry and Neuroscience, Xinxiang Medical University, Henan, China
- DOI
- https://doi.org/10.3389/fimmu.2020.607442
- Journal volume & issue
-
Vol. 11
Abstract
Zdhhc family genes are composed of 24 members that regulate palmitoylation, a post-translational modification process for proteins. Mutations in genes that alter palmitoylation or de-palmitoylation could result in neurodegenerative diseases and inflammatory disorders. In this study, we found that Zdhhc2 was robustly induced in psoriatic skin and loss of Zdhhc2 in mice by CRISPR/Cas9 dramatically inhibited pathology of the ear skin following imiquimod treatment. As psoriasis is an inflammatory disorder, we analyzed tissue infiltrating immune cells and cytokine production. Strikingly we found that a master psoriatic cytokine interferon-α (IFN-α) in the lesioned skin of wildtype (WT) mice was 23-fold higher than that in Zdhhc2 deficient counterparts. In addition, we found that CD45+ white blood cells (WBC) infiltrating in the skin of Zdhhc2 deficient mice were also significantly reduced. Amelioration in psoriasis and dramatically reduced inflammation of Zdhhc2 deficient mice led us to analyze the cellular components that were affected by loss of Zdhhc2. We found that imiquimod induced plasmacytoid dendritic cell (pDC) accumulation in psoriatic skin, spleen, and draining lymph nodes (DLN) were drastically decreased in Zdhhc2 deficient mice, and the expression of pDC activation marker CD80 also exhibited significantly inhibited in psoriatic skin. In further experiments, we confirmed the cell intrinsic effect of Zdhhc2 on pDCs as we found that loss of zDHHC2 in human CAL-1 pDC dampened both interferon regulatory factor 7 (IRF7) phosphorylation and IFN-α production. Therefore, we identified novel function of Zdhhc2 in controlling inflammatory response in psoriasis in mice and we also confirmed that crucial role of Zdhhc2 in pDCs by regulating IRF7 activity and production of the critical cytokine. Our results finding the dependence of IFN-α production on Zdhhc2 in inflamed murine skin and in human pDCs provide rationale for targeting this new molecule in treatment of inflammation.
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