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      Transcriptome Analysis and Emerging Driver Identification of CD8+ T Cells in Patients with Vitiligo

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          Abstract

          Activated CD8+ T cells play important roles in the pathogenesis of vitiligo. However, driving factors about the activation and migration of CD8+ T cells remain obscure. In this study, we aim to identify differentially expressed genes (DEGs) and uncover potential factors that drive the disease in melanocyte-specific CD8+ T cells in vitiligo. A total of 1147 DEGs were found through transcriptome sequencing in CD8+ T cells from lesional skin of vitiligo patients and normal controls. Based on KEGG pathway enrichment analysis and PPI, 16 upregulated and 23 downregulated genes were identified. Ultimately, 3 genes were figured out after RT-qPCR verification. The mRNA and protein expression levels of PIK3CB, HIF-1 α, and F2RL1 were all elevated in CD8+ T cells from peripheral blood in vitiligo. HIF-1 α and PIK3CB were significantly increased in lesional skin of vitiligo. Two CpG sites of the HIF-1 α promoter were hypomethylated in vitiligo CD8+ T cells. In conclusion, HIF-1 α, F2RL1, and PIK3CB may act as novel drivers for vitiligo, which are all closely associated with reactive oxygen species and possibly contribute to the activation and/or migration of melanocyte-specific CD8+ T cells in vitiligo. In addition, we uncovered a potential role for DNA hypomethylation of HIF-1 α in CD8+ T cells of vitiligo.

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          Vitiligo

          Vitiligo, an acquired pigmentary disorder of unknown origin, is the most frequent cause of depigmentation worldwide, with an estimated prevalence of 1%. The disorder can be psychologically devastating and stigmatising, especially in dark skinned individuals. Vitiligo is clinically characterised by the development of white macules due to the loss of functioning melanocytes in the skin or hair, or both. Two forms of the disease are well recognised: segmental and non-segmental vitiligo (the commonest form). To distinguish between these two forms is of prime importance because therapeutic options and prognosis are quite different. The importance of early treatment and understanding of the profound psychosocial effect of vitiligo will be emphasised throughout this Seminar.
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            HIF-1alpha expression regulates the bactericidal capacity of phagocytes.

            Hypoxia is a characteristic feature of the tissue microenvironment during bacterial infection. Here we report on our use of conditional gene targeting to examine the contribution of hypoxia-inducible factor 1, alpha subunit (HIF-1alpha) to myeloid cell innate immune function. HIF-1alpha was induced by bacterial infection, even under normoxia, and regulated the production of key immune effector molecules, including granule proteases, antimicrobial peptides, nitric oxide, and TNF-alpha. Mice lacking HIF-1alpha in their myeloid cell lineage showed decreased bactericidal activity and failed to restrict systemic spread of infection from an initial tissue focus. Conversely, activation of the HIF-1alpha pathway through deletion of von Hippel-Lindau tumor-suppressor protein or pharmacologic inducers supported myeloid cell production of defense factors and improved bactericidal capacity. HIF-1alpha control of myeloid cell activity in infected tissues could represent a novel therapeutic target for enhancing host defense.
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              HIF-1α Is Essential for Myeloid Cell-Mediated Inflammation

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                Author and article information

                Contributors
                Journal
                Oxid Med Cell Longev
                Oxid Med Cell Longev
                OMCL
                Oxidative Medicine and Cellular Longevity
                Hindawi
                1942-0900
                1942-0994
                2019
                26 November 2019
                : 2019
                : 2503924
                Affiliations
                1Department of Dermatology, Second Xiangya Hospital, Central South University, Hunan Key Laboratory of Medical Epigenetics, Changsha, China
                2Department of Urology, Third Xiangya Hospital of Central South University, Changsha, China
                3Department of Anesthesiology, Second Xiangya Hospital, Central South University, Changsha, China
                4Department of Dermatology, Third Xiangya Hospital of Central South University, Changsha, China
                Author notes

                Academic Editor: Ryoji Nagai

                Author information
                https://orcid.org/0000-0002-9360-7180
                https://orcid.org/0000-0002-1037-7990
                https://orcid.org/0000-0002-6214-8057
                Article
                10.1155/2019/2503924
                6899274
                31885781
                5b72459e-3dbe-4e08-a3d5-2abd90b8b1b1
                Copyright © 2019 Qiancheng Deng et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 25 September 2019
                : 9 November 2019
                Funding
                Funded by: National Natural Science Foundation of China
                Award ID: 81703134
                Award ID: 81502725
                Award ID: 81773333
                Award ID: 81371744
                Categories
                Research Article

                Molecular medicine
                Molecular medicine

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