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      MicroRNA-155 inhibits the proliferation of CD8 + T cells via upregulating regulatory T cells in vitiligo

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          Abstract

          It has been reported that loss and degradation of epidermal melanocytes is closely associated with the pathogenesis of vitiligo. In addition, CD8 + T and regulatory T (Treg) cells serve an important role during these two processes. MicroRNA-155 (miR-155) is known to contribute to the pathogenesis of vitiligo; however, the mechanism by which miR-155 regulates the development of vitiligo remains unclear. In the present study, naïve T and CD8 + T cells were isolated from a patient with non-segmental vitiligo by flow cytometry. The cells were differentiated into Treg cells by treatment with interleukin-2, transforming growth factor-β and retinoic acid. In addition, miR-155 agonists and antagonists were used to investigate the effect of miR-155 on the proliferation of CD8 + T cells, Treg cells and melanocytes. The results demonstrated that the miR-155 agonist significantly decreased the rate of CD8 + T cell growth, as well as promoted the proliferation of melanocytes by inducing an increase in the percentage of Treg cells. By contrast, the miR-155 antagonist inhibited the proliferation of melanocytes by decreasing the percentage of Treg cells. miR-155 protected melanocyte survival by increasing the number of Treg cells and by decreasing the number of CD8 + T cells. Therefore, these data may provide a new prospect for the treatment of vitiligo.

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          Most cited references32

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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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            MicroRNA in autoimmunity and autoimmune diseases.

            MicroRNAs (miRNAs) are small conserved non-coding RNA molecules that post-transcriptionally regulate gene expression by targeting the 3' untranslated region (UTR) of specific messenger RNAs (mRNAs) for degradation or translational repression. miRNA-mediated gene regulation is critical for normal cellular functions such as the cell cycle, differentiation, and apoptosis, and as much as one-third of human mRNAs may be miRNA targets. Emerging evidence has demonstrated that miRNAs play a vital role in the regulation of immunological functions and the prevention of autoimmunity. Here we review the many newly discovered roles of miRNA regulation in immune functions and in the development of autoimmunity and autoimmune disease. Specifically, we discuss the involvement of miRNA regulation in innate and adaptive immune responses, immune cell development, T regulatory cell stability and function, and differential miRNA expression in rheumatoid arthritis and systemic lupus erythematosus.
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              Autoimmune destruction of skin melanocytes by perilesional T cells from vitiligo patients.

              In vitiligo, cytotoxic T cells infiltrating the perilesional margin are suspected to be involved in the pathogenesis of the disease. However, it remains to be elucidated whether these T cells are a cause or a consequence of the depigmentation process. T cells we obtained from perilesional skin biopsies, were significantly enriched for melanocyte antigen recognition, compared with healthy skin-infiltrating T cells, and were reactive to melanocyte antigen-specific stimulation. Using a skin explant model, we were able to dissect the in situ activities of perilesional T cells in the effector phase of depigmentation. We show that these T cells could infiltrate autologous normally pigmented skin explants and efficiently kill melanocytes within this microenvironment. Interestingly, melanocyte apoptosis was accompanied by suprabasal keratinocyte apoptosis. Perilesional T cells did, however, not induce apoptosis in lesional skin, which is devoid of melanocytes, indicating the melanocyte-specific cytotoxic activity of these cells. Melanocyte killing correlated to local infiltration of perilesional T cells. Our data show that perilesional cytotoxic T cells eradicate pigment cells, the characteristic hallmark of vitiligo, thereby providing evidence of T cells being able to mediate targeted autoimmune tissue destruction.
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                Author and article information

                Journal
                Mol Med Rep
                Mol Med Rep
                Molecular Medicine Reports
                D.A. Spandidos
                1791-2997
                1791-3004
                October 2019
                23 August 2019
                23 August 2019
                : 20
                : 4
                : 3617-3624
                Affiliations
                [1 ]Department of Dermatology, Qilu Hospital, Shandong University, Jinan, Shandong 250012, P.R. China
                [2 ]Department of Dermatology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China
                [3 ]Department of Dermatology, Jinan Central Hospital, Jinan, Shandong 250013, P.R. China
                Author notes
                Correspondence to: Dr Keyu Wang, Department of Dermatology, Qilu Hospital, Shandong University, 107 Wenhua West Road, Jinan, Shandong 250012, P.R. China, E-mail: qlyywky@ 123456163.com
                Dr Yunsheng Xu, Department of Dermatology, The First Affiliated Hospital of Wenzhou Medical University, 2 Fuxiang Alley, Lucheng, Wenzhou, Zhejiang 325000, P.R. China, E-mail: xuyunsheng1018@ 123456163.com
                Article
                mmr-20-04-3617
                10.3892/mmr.2019.10607
                6755204
                31485649
                98e76b47-41b3-4f59-8ce0-b931a22d78ee
                Copyright: © Lv et al.

                This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

                History
                : 31 January 2019
                : 11 July 2019
                Categories
                Articles

                vitiligo,microrna-155,regulatory t cells,cd8+ t cells
                vitiligo, microrna-155, regulatory t cells, cd8+ t cells

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