{"title":"异位培养和诱导T淋巴细胞的胸腺类器官的发育","authors":"Xiuxia Wang, Shun Yu, Yucheng Qiu, Jun Yang, Fei Liu, Xianyu Zhou","doi":"10.1002/iid3.70229","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> Background</h3>\n \n <p>Vascularized composite allotransplantation (VCA) is a potential treatment for extensive injuries that replaces defects like-with-like, however allografts are immune-rejectable.</p>\n </section>\n \n <section>\n \n <h3> Methods</h3>\n \n <p>This study developed in vitro thymic organoids and examined whether donor-derived HSCs could be educated in vivo into T lymphocytes via central tolerance. TECs, TMCs, and HSCs from C57BL/7 (CD45.2<sup>+</sup>) or SJL/L (CD45.1<sup>+</sup>) mice were labeled with cell surface markers and examined by flow cytometry. Co-culturing three cell lines in vitro created thymic aggregates. Aggregates transplanted to C57BL/7 (CD45.2<sup>+</sup>) mice′s inguinal regions developed thymic organoids. Immunorejection genes were identified bioinformatically. Western blot, immunofluorescence, and flow cytometry were utilized to measure rejection-related protein levels and T cell surface markers in thymic organoids to determine T cell inducement and immunomodulation.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>In vitro, TECs, TMCs, and HSCs created thymic aggregates, which became thymic organoids after in vivo transplantation and produced CD8<sup>+</sup> and CD4<sup>+</sup> Tregs. Bioinformatics showed high correlations between transplanted rejection and IFNG, IL2RG, FCGR3A, and ICAM1 genes. Immunofluorescence and Western blot showed increased protein expression of IFNG, IL2RG, FCGR3A (immunomodulation biomarker), and decreased protein expression of CK8, CK14, and ICAM1 (TEC biomarker) in thymic organoids.</p>\n </section>\n \n <section>\n \n <h3> Conclusion</h3>\n \n <p>Thymic organoids heterotopically implanted in vivo can promote heterologous HSC-derived T cell development.</p>\n </section>\n </div>","PeriodicalId":13289,"journal":{"name":"Immunity, Inflammation and Disease","volume":"13 8","pages":""},"PeriodicalIF":2.7000,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/iid3.70229","citationCount":"0","resultStr":"{\"title\":\"Development of Thymic Organoids Heterotopically to Educate and Induce T Lymphocytes\",\"authors\":\"Xiuxia Wang, Shun Yu, Yucheng Qiu, Jun Yang, Fei Liu, Xianyu Zhou\",\"doi\":\"10.1002/iid3.70229\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n \\n <section>\\n \\n <h3> Background</h3>\\n \\n <p>Vascularized composite allotransplantation (VCA) is a potential treatment for extensive injuries that replaces defects like-with-like, however allografts are immune-rejectable.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Methods</h3>\\n \\n <p>This study developed in vitro thymic organoids and examined whether donor-derived HSCs could be educated in vivo into T lymphocytes via central tolerance. TECs, TMCs, and HSCs from C57BL/7 (CD45.2<sup>+</sup>) or SJL/L (CD45.1<sup>+</sup>) mice were labeled with cell surface markers and examined by flow cytometry. Co-culturing three cell lines in vitro created thymic aggregates. Aggregates transplanted to C57BL/7 (CD45.2<sup>+</sup>) mice′s inguinal regions developed thymic organoids. Immunorejection genes were identified bioinformatically. Western blot, immunofluorescence, and flow cytometry were utilized to measure rejection-related protein levels and T cell surface markers in thymic organoids to determine T cell inducement and immunomodulation.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Results</h3>\\n \\n <p>In vitro, TECs, TMCs, and HSCs created thymic aggregates, which became thymic organoids after in vivo transplantation and produced CD8<sup>+</sup> and CD4<sup>+</sup> Tregs. Bioinformatics showed high correlations between transplanted rejection and IFNG, IL2RG, FCGR3A, and ICAM1 genes. Immunofluorescence and Western blot showed increased protein expression of IFNG, IL2RG, FCGR3A (immunomodulation biomarker), and decreased protein expression of CK8, CK14, and ICAM1 (TEC biomarker) in thymic organoids.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Conclusion</h3>\\n \\n <p>Thymic organoids heterotopically implanted in vivo can promote heterologous HSC-derived T cell development.</p>\\n </section>\\n </div>\",\"PeriodicalId\":13289,\"journal\":{\"name\":\"Immunity, Inflammation and Disease\",\"volume\":\"13 8\",\"pages\":\"\"},\"PeriodicalIF\":2.7000,\"publicationDate\":\"2025-08-22\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://onlinelibrary.wiley.com/doi/epdf/10.1002/iid3.70229\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Immunity, Inflammation and Disease\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1002/iid3.70229\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"IMMUNOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Immunity, Inflammation and Disease","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/iid3.70229","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
Development of Thymic Organoids Heterotopically to Educate and Induce T Lymphocytes
Background
Vascularized composite allotransplantation (VCA) is a potential treatment for extensive injuries that replaces defects like-with-like, however allografts are immune-rejectable.
Methods
This study developed in vitro thymic organoids and examined whether donor-derived HSCs could be educated in vivo into T lymphocytes via central tolerance. TECs, TMCs, and HSCs from C57BL/7 (CD45.2+) or SJL/L (CD45.1+) mice were labeled with cell surface markers and examined by flow cytometry. Co-culturing three cell lines in vitro created thymic aggregates. Aggregates transplanted to C57BL/7 (CD45.2+) mice′s inguinal regions developed thymic organoids. Immunorejection genes were identified bioinformatically. Western blot, immunofluorescence, and flow cytometry were utilized to measure rejection-related protein levels and T cell surface markers in thymic organoids to determine T cell inducement and immunomodulation.
Results
In vitro, TECs, TMCs, and HSCs created thymic aggregates, which became thymic organoids after in vivo transplantation and produced CD8+ and CD4+ Tregs. Bioinformatics showed high correlations between transplanted rejection and IFNG, IL2RG, FCGR3A, and ICAM1 genes. Immunofluorescence and Western blot showed increased protein expression of IFNG, IL2RG, FCGR3A (immunomodulation biomarker), and decreased protein expression of CK8, CK14, and ICAM1 (TEC biomarker) in thymic organoids.
Conclusion
Thymic organoids heterotopically implanted in vivo can promote heterologous HSC-derived T cell development.
期刊介绍：
Immunity, Inflammation and Disease is a peer-reviewed, open access, interdisciplinary journal providing rapid publication of research across the broad field of immunology. Immunity, Inflammation and Disease gives rapid consideration to papers in all areas of clinical and basic research. The journal is indexed in Medline and the Science Citation Index Expanded (part of Web of Science), among others. It welcomes original work that enhances the understanding of immunology in areas including:
• cellular and molecular immunology
• clinical immunology
• allergy
• immunochemistry
• immunogenetics
• immune signalling
• immune development
• imaging
• mathematical modelling
• autoimmunity
• transplantation immunology
• cancer immunology
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