Shikonin impairs T lymphocyte proliferation and thymopoiesis while it may increase myeloid-derived suppressor cells to alleviate immune responses |
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| Institution: | 1. Department of Oncology, The First Hospital, Jilin University, Changchun 130021, China;2. Key Laboratory of Organ Regeneration & Transplantation of the Ministry of Education, The First Hospital, Jilin University; Changchun, 130061, China;3. National-Local Joint Engineering Laboratory of Animal Models for Human Diseases, Changchun 130061, China;4. Department of Hematology, The First Hospital, Jilin University, Changchun 130021, China;1. Department of Hematology, Atomic Bomb Disease and Hibakusha Medicine Unit, Nagasaki University Graduate School of Biomedical Science, Nagasaki, Japan;2. Department of Hematology, Sasebo City General Hospital, Sasebo, Japan;3. Department of Hematology, Nagasaki University Hospital, Nagasaki, Japan;4. Department of Hematology, National Hospital Organization Nagasaki Medical Center, Omura, Japan;5. Department of Hematology, Atomic Bomb Disease and Hibakusha Medicine Unit, Atomic Bomb Disease Institute, Nagasaki University, Nagasaki, Japan;6. Department of Hematology, Japanese Red Cross Nagasaki Genbaku Hospital, Nagasaki, Japan;1. Neurological Surgery Department, University of São Paulo, School of Medicine, São Paulo, Brazil;2. Organ Procurement Organization, Hospital das Clínicas, University of São Paulo, School of Medicine, São Paulo, Brazil;3. Gastroenterology Department, University of São Paulo, School of Medicine, São Paulo, Brazil;4. Medical Science Department, Nove de Julho University, São Paulo, Brazil;5. Cardiopneumology Department, University of São Paulo, School of Medicine, São Paulo, Brazil;6. School of Nursing of the University of São Paulo, São Paulo, Brazil;1. Fédération des Spécialités Digestives, Hôpital Edouard Herriot, Hospices civils de Lyon, Lyon, France;2. Université Claude Bernard Lyon 1, Lyon, France;3. Service d''hépatologie et de Transplantation Hépatique, Hôpital de la Croix Rousse, Hospices Civils de Lyon, Lyon, France;4. Service des Maladies de l''Appareil Digestif, Hôpital Claude Huriez, CHRU Lille, Lille, France;5. Centre Hépato-Biliaire, Hôpital Paul Brousse, AP-HP, Villejuif, France;6. Département de Néphrologie et Transplantation d''Organes, CHU Rangueil, Toulouse, France;1. Department of Nephrology and Renal Transplantation, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India;2. Department of Urology Renal Transplantation, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India;1. Division of Hematology with BMT, A.O.U. “Policlinico-San Marco”, Via S. Sofia 78, 95123 Catania, Italy;2. Onco-Hematology and BMT Unit, “Mediterranean Institute of Oncology”, Viagrande, Italy;3. Division of Nephrology, A.O.U. Policlinico “G. Rodolico-San Marco”, Catania, Italy;1. Department of Renal Surgery and Transplantation, Jichi Medical University Hospital, Tochigi, Japan;2. Department of Orthopaedics, Teikyo University School of Medicine, Tokyo, Japan;3. Oku medical clinic, Osaka, Japan;4. Scientific Research WorkS Peer Support Group (SRWS-PSG), Osaka, Japan |
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| Abstract: | Shikonin (SHK) has multifaceted physiological functions, including antitumor, anti-inflammatory, and antimicrobial effects. Recently, SHK has been shown to affect immune responses; however, its detailed immune modulatory function in vivo remains unclear. In this study, we demonstrated that SHK not only inhibited T cell proliferation in vitro, but also intensively inhibited thymopoiesis and eliminated CD4/CD8 double-positive thymic progenitor cells in vivo. Treatment of mice with SHK resulted in immune profile alterations, which promoted myelosis in the bone marrow and increased inhibitory immune cells in central immune organs. A decrease in T cells and B cells was observed in the spleen. Using a murine allogenic skin transplantation model, we revealed that short-term treatment of recipients with SHK significantly inhibited skin graft rejection, in which the levels of myeloid-derived suppressor cells (MDSC) were markedly increased. Taken together, our study suggests that SHK can efficiently eliminate proliferating T cells and inhibit thymopoiesis while promoting the generation of MDSC, indicating its potential role in alleviating immune responses in allogeneic organ/cell transplantation. |
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