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      T cell–derived exosomes induced macrophage inflammatory protein‐1α/β drive the trafficking of CD8 + T cells in oral lichen planus

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          Abstract

          Oral lichen planus (OLP) is a T cell–mediated chronic inflammatory disease with uncertain aetiology. Exosomes are nanosized particles with biological capacities. Here, we aimed to study the effects of T cell–derived exosomes (T‐exos) on the pathogenesis of OLP and its mechanism. T‐exos were incubated with Jurkat cells for 48 hours, and 26 cytokines in the supernatant were measured by luminex assay. The expression of macrophage inflammatory protein (MIP)‐1α/β was detected using immunohistochemistry and ELISA; that of CCR1/3/5 on peripheral T cells was determined by flow cytometry. Transwell assay was performed to investigate the chemotactic effect of MIP‐1α/β, and cells in the lower chambers were examinated by flow cytometry. As a result, OLP T‐exos elevated the production of MIP‐1α/β, which were highly expressed in OLP tissues and plasma. CCR1/5 were markedly expressed on OLP peripheral T cells, and the majority of CCR1/5 + T cells were CD8 + T cells. Besides, MIP‐1α/β promoted the migration of OLP mononuclear cells, while inhibiting CCR1/5 significantly decreased the trafficking of mononuclear cells, especially that of CD8 + T cells. Conclusively, OLP T‐exos‐induced MIP‐1α/β may drive the trafficking of CD8 + T cells after binding with CCR1/5 in OLP, contributing to the development of OLP.

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          Most cited references38

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          Shedding light on the cell biology of extracellular vesicles

          Extracellular vesicles are a heterogeneous group of cell-derived membranous structures comprising exosomes and microvesicles, which originate from the endosomal system or which are shed from the plasma membrane, respectively. They are present in biological fluids and are involved in multiple physiological and pathological processes. Extracellular vesicles are now considered as an additional mechanism for intercellular communication, allowing cells to exchange proteins, lipids and genetic material. Knowledge of the cellular processes that govern extracellular vesicle biology is essential to shed light on the physiological and pathological functions of these vesicles as well as on clinical applications involving their use and/or analysis. However, in this expanding field, much remains unknown regarding the origin, biogenesis, secretion, targeting and fate of these vesicles.
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            Biogenesis, secretion, and intercellular interactions of exosomes and other extracellular vesicles.

            In the 1980s, exosomes were described as vesicles of endosomal origin secreted from reticulocytes. Interest increased around these extracellular vesicles, as they appeared to participate in several cellular processes. Exosomes bear proteins, lipids, and RNAs, mediating intercellular communication between different cell types in the body, and thus affecting normal and pathological conditions. Only recently, scientists acknowledged the difficulty of separating exosomes from other types of extracellular vesicles, which precludes a clear attribution of a particular function to the different types of secreted vesicles. To shed light into this complex but expanding field of science, this review focuses on the definition of exosomes and other secreted extracellular vesicles. Their biogenesis, their secretion, and their subsequent fate are discussed, as their functions rely on these important processes.
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              Exosomal PD-L1 Contributes to Immunosuppression and is Associated with anti-PD-1 Response

              Tumor cells evade the immune surveillance by up-regulating surface expression of PD-L1, which interacts with PD-1 on T cells to elicit the immune checkpoint response 1,2 . Anti-PD-1 antibodies have shown remarkable promise in treating tumors, including metastatic melanoma 2–4 . However, patient response rate is low 4,5 . A better understanding of PD-L1-mediated immune evasion is needed to predict patient response and improve treatment efficacy. Here we report that metastatic melanoma releases a high level of extracellular vesicles (EVs), mostly in the form of exosomes, that carry PD-L1 on their surface. Interferon-γ (IFN-γ) up-regulates PD-L1 on these vesicles, which suppresses the function of CD8 T cells and facilitates tumor growth. In patients with metastatic melanoma, the level of circulating exosomal PD-L1 positively correlates with that of IFN-γ, and changes during the course of anti-PD-1 therapy. The magnitudes of the early on-treatment increase in circulating exosomal PD-L1, as an indicator of the adaptive response of the tumor cells to T cell re-invigoration, stratifies clinical responders from non-responders. Our study unveils a mechanism by which tumor cells systemically suppress the immune system, and provides a rationale for the application of exosomal PD-L1 as a predictor for anti-PD-1 therapy.
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                Author and article information

                Contributors
                zhougang@whu.edu.cn
                Journal
                J Cell Mol Med
                J Cell Mol Med
                10.1111/(ISSN)1582-4934
                JCMM
                Journal of Cellular and Molecular Medicine
                John Wiley and Sons Inc. (Hoboken )
                1582-1838
                1582-4934
                27 October 2020
                December 2020
                : 24
                : 23 ( doiID: 10.1111/jcmm.v24.23 )
                : 14086-14098
                Affiliations
                [ 1 ] The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei‐MOST) and Key Laboratory of Oral Biomedicine Ministry of Education School and Hospital of Stomatology Wuhan University Wuhan China
                [ 2 ] Department of Oral Medicine School and Hospital of Stomatology Wuhan University Wuhan China
                Author notes
                [*] [* ] Correspondence

                Gang Zhou, Department of Oral Medicine, School and Hospital of Stomatology, Wuhan University, Luoyu Road 237, Wuhan, China.

                Email: zhougang@ 123456whu.edu.cn

                Author information
                https://orcid.org/0000-0002-1475-6701
                https://orcid.org/0000-0002-8651-7638
                https://orcid.org/0000-0001-6883-5643
                https://orcid.org/0000-0001-7629-9334
                https://orcid.org/0000-0002-9522-0887
                https://orcid.org/0000-0003-4988-0814
                Article
                JCMM16020
                10.1111/jcmm.16020
                7754044
                33107682
                cf6eb1e1-e906-44f6-b398-3d5dde7af883
                © 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 10 July 2020
                : 22 September 2020
                : 06 October 2020
                Page count
                Figures: 5, Tables: 3, Pages: 13, Words: 6487
                Funding
                Funded by: National Natural Science Foundation of China , open-funder-registry 10.13039/501100001809;
                Award ID: 81771080
                Award ID: 81970949
                Award ID: 81371147
                Funded by: State Key Laboratory of Oral Diseases , open-funder-registry 10.13039/501100011262;
                Award ID: SKLOD2020OF01
                Categories
                Original Article
                Original Articles
                Custom metadata
                2.0
                December 2020
                Converter:WILEY_ML3GV2_TO_JATSPMC version:5.9.6 mode:remove_FC converted:22.12.2020

                Molecular medicine
                exosome,macrophage inflammatory protein‐1α/β,migration,oral lichen planus,t cell

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