IL‐10 producing type 2 innate lymphoid cells prolong islet allograft survival
Abstract Type 2 innate lymphoid cells (ILC2s) are a subset of ILCs with critical roles in immunoregulation. However, the possible role of ILC2s as immunotherapy against allograft rejection remains unclear. Here, we show that IL‐33 significantly prolonged islet allograft survival. IL‐33‐treated mice...
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| Format: | Article |
| Language: | English |
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Springer Nature
2020-10-01
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| Series: | EMBO Molecular Medicine |
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| Online Access: | https://doi.org/10.15252/emmm.202012305 |
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| author | Qingsong Huang Xiaoqian Ma Yiping Wang Zhiguo Niu Ruifeng Wang Fuyan Yang Menglin Wu Guining Liang Pengfei Rong Hui Wang David CH Harris Wei Wang Qi Cao |
| author_facet | Qingsong Huang Xiaoqian Ma Yiping Wang Zhiguo Niu Ruifeng Wang Fuyan Yang Menglin Wu Guining Liang Pengfei Rong Hui Wang David CH Harris Wei Wang Qi Cao |
| author_sort | Qingsong Huang |
| collection | DOAJ |
| description | Abstract Type 2 innate lymphoid cells (ILC2s) are a subset of ILCs with critical roles in immunoregulation. However, the possible role of ILC2s as immunotherapy against allograft rejection remains unclear. Here, we show that IL‐33 significantly prolonged islet allograft survival. IL‐33‐treated mice had elevated numbers of ILC2s and regulatory T cells (Tregs). Depletion of Tregs partially abolished the protective effect of IL‐33 on allograft survival, and additional ILC2 depletion in Treg‐depleted DEREG mice completely abolished the protective effects of IL‐33, indicating that ILC2s play critical roles in IL‐33‐mediated islet graft protection. Two subsets of ILC2s were identified in islet allografts of IL‐33‐treated mice: IL‐10 producing ILC2s (ILC210) and non‐IL‐10 producing ILC2s (non‐ILC10). Intravenous transfer of ILC210 cells, but not non‐ILC10, prolonged islet allograft survival in an IL‐10‐dependent manner. Locally transferred ILC210 cells led to long‐term islet graft survival, suggesting that ILC210 cells are required within the allograft for maximal suppressive effect and graft protection. This study has uncovered a major protective role of ILC210 in islet transplantation which could be potentiated as a therapeutic strategy. |
| format | Article |
| id | doaj-art-320719088d8345a3bd5bee075c9d2015 |
| institution | Kabale University |
| issn | 1757-4676 1757-4684 |
| language | English |
| publishDate | 2020-10-01 |
| publisher | Springer Nature |
| record_format | Article |
| series | EMBO Molecular Medicine |
| spelling | doaj-art-320719088d8345a3bd5bee075c9d20152025-08-20T03:43:26ZengSpringer NatureEMBO Molecular Medicine1757-46761757-46842020-10-01121111610.15252/emmm.202012305IL‐10 producing type 2 innate lymphoid cells prolong islet allograft survivalQingsong Huang0Xiaoqian Ma1Yiping Wang2Zhiguo Niu3Ruifeng Wang4Fuyan Yang5Menglin Wu6Guining Liang7Pengfei Rong8Hui Wang9David CH Harris10Wei Wang11Qi Cao12Henan Key Laboratory of Immunology and Targeted Drugs, School of Laboratory Medicine, Xinxiang Medical UniversityCentre for Transplant and Renal Research, Westmead Institute for Medical Research, The University of SydneyCentre for Transplant and Renal Research, Westmead Institute for Medical Research, The University of SydneyHenan Key Laboratory of Immunology and Targeted Drugs, School of Laboratory Medicine, Xinxiang Medical UniversityCentre for Transplant and Renal Research, Westmead Institute for Medical Research, The University of SydneyThe Department of Nephrology, First People's Hospital of Xinxiang Medical UniversityHenan Key Laboratory of Immunology and Targeted Drugs, School of Laboratory Medicine, Xinxiang Medical UniversityThe Department of Physiology, Guangxi Medical UniversityThe Institute for Cell Transplantation and Gene Therapy, The Third Xiangya Hospital of Central South UniversityHenan Key Laboratory of Immunology and Targeted Drugs, School of Laboratory Medicine, Xinxiang Medical UniversityCentre for Transplant and Renal Research, Westmead Institute for Medical Research, The University of SydneyThe Institute for Cell Transplantation and Gene Therapy, The Third Xiangya Hospital of Central South UniversityHenan Key Laboratory of Immunology and Targeted Drugs, School of Laboratory Medicine, Xinxiang Medical UniversityAbstract Type 2 innate lymphoid cells (ILC2s) are a subset of ILCs with critical roles in immunoregulation. However, the possible role of ILC2s as immunotherapy against allograft rejection remains unclear. Here, we show that IL‐33 significantly prolonged islet allograft survival. IL‐33‐treated mice had elevated numbers of ILC2s and regulatory T cells (Tregs). Depletion of Tregs partially abolished the protective effect of IL‐33 on allograft survival, and additional ILC2 depletion in Treg‐depleted DEREG mice completely abolished the protective effects of IL‐33, indicating that ILC2s play critical roles in IL‐33‐mediated islet graft protection. Two subsets of ILC2s were identified in islet allografts of IL‐33‐treated mice: IL‐10 producing ILC2s (ILC210) and non‐IL‐10 producing ILC2s (non‐ILC10). Intravenous transfer of ILC210 cells, but not non‐ILC10, prolonged islet allograft survival in an IL‐10‐dependent manner. Locally transferred ILC210 cells led to long‐term islet graft survival, suggesting that ILC210 cells are required within the allograft for maximal suppressive effect and graft protection. This study has uncovered a major protective role of ILC210 in islet transplantation which could be potentiated as a therapeutic strategy.https://doi.org/10.15252/emmm.202012305IL‐10IL‐33innate lymphoid cellsislet transplantationtype 1 diabetes |
| spellingShingle | Qingsong Huang Xiaoqian Ma Yiping Wang Zhiguo Niu Ruifeng Wang Fuyan Yang Menglin Wu Guining Liang Pengfei Rong Hui Wang David CH Harris Wei Wang Qi Cao IL‐10 producing type 2 innate lymphoid cells prolong islet allograft survival EMBO Molecular Medicine IL‐10 IL‐33 innate lymphoid cells islet transplantation type 1 diabetes |
| title | IL‐10 producing type 2 innate lymphoid cells prolong islet allograft survival |
| title_full | IL‐10 producing type 2 innate lymphoid cells prolong islet allograft survival |
| title_fullStr | IL‐10 producing type 2 innate lymphoid cells prolong islet allograft survival |
| title_full_unstemmed | IL‐10 producing type 2 innate lymphoid cells prolong islet allograft survival |
| title_short | IL‐10 producing type 2 innate lymphoid cells prolong islet allograft survival |
| title_sort | il 10 producing type 2 innate lymphoid cells prolong islet allograft survival |
| topic | IL‐10 IL‐33 innate lymphoid cells islet transplantation type 1 diabetes |
| url | https://doi.org/10.15252/emmm.202012305 |
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