Type 2 innate lymphoid cells are protective against hepatic ischaemia/reperfusion injury
Background and Aims: Although type 2 innate lymphoid cells (ILC2s) were originally found to be liver-resident lymphocytes, the role and importance of ILC2 in liver injury remains poorly understood. In the current study, we sought to determine whether ILC2 is an important regulator of hepatic ischaem...
| Main Authors: | , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-10-01
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| Series: | JHEP Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589555923001684 |
| _version_ | 1797706855282114560 |
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| author | Qi Cao Ruifeng Wang Zhiguo Niu Titi Chen Farhana Azmi Scott A. Read Jianwei Chen Vincent W.S. Lee Chunze Zhou Sohel Julovi Qingsong Huang Yuan Min Wang Malcolm R. Starkey Guoping Zheng Stephen I. Alexander Jacob George Yiping Wang David C.H. Harris |
| author_facet | Qi Cao Ruifeng Wang Zhiguo Niu Titi Chen Farhana Azmi Scott A. Read Jianwei Chen Vincent W.S. Lee Chunze Zhou Sohel Julovi Qingsong Huang Yuan Min Wang Malcolm R. Starkey Guoping Zheng Stephen I. Alexander Jacob George Yiping Wang David C.H. Harris |
| author_sort | Qi Cao |
| collection | DOAJ |
| description | Background and Aims: Although type 2 innate lymphoid cells (ILC2s) were originally found to be liver-resident lymphocytes, the role and importance of ILC2 in liver injury remains poorly understood. In the current study, we sought to determine whether ILC2 is an important regulator of hepatic ischaemia/reperfusion injury (IRI). Methods: ILC2-deficient mice (ICOS-T or NSG) and genetically modified ILC2s were used to investigate the role of ILC2s in murine hepatic IRI. Interactions between ILC2s and eosinophils or macrophages were studied in coculture. The role of human ILC2s was assessed in an immunocompromised mouse model of hepatic IRI. Results: Administration of IL-33 prevented hepatic IRI in association with reduction of neutrophil infiltration and inflammatory mediators in the liver. IL-33-treated mice had elevated numbers of ILC2s, eosinophils, and regulatory T cells. Eosinophils, but not regulatory T cells, were required for IL-33-mediated hepatoprotection in IRI mice. Depletion of ILC2s substantially abolished the protective effect of IL-33 in hepatic IRI, indicating that ILC2s play critical roles in IL-33-mediated liver protection. Adoptive transfer of ex vivo-expanded ILC2s improved liver function and attenuated histologic damage in mice subjected to IRI. Mechanistic studies combining genetic and adoptive transfer approaches identified a protective role of ILC2s through promoting IL-13-dependent induction of anti-inflammatory macrophages and IL-5-dependent elevation of eosinophils in IRI. Furthermore, in vivo expansion of human ILC2s by IL-33 or transfer of ex vivo-expanded human ILC2s ameliorated hepatic IRI in an immunocompromised mouse model of hepatic IRI. Conclusions: This study provides insight into the mechanisms of ILC2-mediated liver protection that could serve as therapeutic targets to treat acute liver injury. Impact and Implications: We report that type 2 innate lymphoid cells (ILC2s) are important regulators in a mouse model of liver ischaemia/reperfusion injury (IRI). Through manipulation of macrophage and eosinophil phenotypes, ILC2s mitigate liver inflammation and injury during liver IRI. We propose that ILC2s have the potential to serve as a therapeutic tool for protecting against acute liver injury and lay the foundation for translation of ILC2 therapy to human liver disease. |
| first_indexed | 2024-03-12T05:58:34Z |
| format | Article |
| id | doaj.art-69039427e9784e949ef473beddbc32b2 |
| institution | Directory Open Access Journal |
| issn | 2589-5559 |
| language | English |
| last_indexed | 2024-03-12T05:58:34Z |
| publishDate | 2023-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | JHEP Reports |
| spelling | doaj.art-69039427e9784e949ef473beddbc32b22023-09-03T04:24:24ZengElsevierJHEP Reports2589-55592023-10-01510100837Type 2 innate lymphoid cells are protective against hepatic ischaemia/reperfusion injuryQi Cao0Ruifeng Wang1Zhiguo Niu2Titi Chen3Farhana Azmi4Scott A. Read5Jianwei Chen6Vincent W.S. Lee7Chunze Zhou8Sohel Julovi9Qingsong Huang10Yuan Min Wang11Malcolm R. Starkey12Guoping Zheng13Stephen I. Alexander14Jacob George15Yiping Wang16David C.H. Harris17Centre for Transplant and Renal Research, Westmead Institute for Medical Research, The University of Sydney, Sydney, NSW, Australia; Corresponding authors. Address: Centre for Transplant and Renal Research, Westmead Institute for Medical Research, The University of Sydney, Sydney, NSW, Australia. Tel.: +61 02 86273512.Centre for Transplant and Renal Research, Westmead Institute for Medical Research, The University of Sydney, Sydney, NSW, Australia; Department of Nephrology, The Second Hospital of Anhui Medical University, Hefei, ChinaHenan Key Laboratory of Immunology and Targeted Drugs, School of Laboratory Medicine, Xinxiang Medical University, Xinxiang, ChinaCentre for Transplant and Renal Research, Westmead Institute for Medical Research, The University of Sydney, Sydney, NSW, AustraliaCentre for Transplant and Renal Research, Westmead Institute for Medical Research, The University of Sydney, Sydney, NSW, AustraliaStorr Liver Centre, Westmead Institute for Medical Research, The University of Sydney, Sydney, NSW, AustraliaCentre for Transplant and Renal Research, Westmead Institute for Medical Research, The University of Sydney, Sydney, NSW, AustraliaCentre for Transplant and Renal Research, Westmead Institute for Medical Research, The University of Sydney, Sydney, NSW, AustraliaDepartment of Interventional Radiology, The First Affiliated Hospital of University of Science and Technology of China, Hefei, ChinaCentre for Transplant and Renal Research, Westmead Institute for Medical Research, The University of Sydney, Sydney, NSW, AustraliaHenan Key Laboratory of Immunology and Targeted Drugs, School of Laboratory Medicine, Xinxiang Medical University, Xinxiang, ChinaCentre for Kidney Research, Children’s Hospital at Westmead, Sydney, NSW, AustraliaDepartment of Immunology and Pathology, Central Clinical School, Monash University, Melbourne, VIC, AustraliaCentre for Transplant and Renal Research, Westmead Institute for Medical Research, The University of Sydney, Sydney, NSW, AustraliaCentre for Kidney Research, Children’s Hospital at Westmead, Sydney, NSW, AustraliaStorr Liver Centre, Westmead Institute for Medical Research, The University of Sydney, Sydney, NSW, AustraliaCentre for Transplant and Renal Research, Westmead Institute for Medical Research, The University of Sydney, Sydney, NSW, AustraliaCentre for Transplant and Renal Research, Westmead Institute for Medical Research, The University of Sydney, Sydney, NSW, Australia; Corresponding authors. Address: Centre for Transplant and Renal Research, Westmead Institute for Medical Research, The University of Sydney, Sydney, NSW, Australia. Tel.: +61 02 86273512.Background and Aims: Although type 2 innate lymphoid cells (ILC2s) were originally found to be liver-resident lymphocytes, the role and importance of ILC2 in liver injury remains poorly understood. In the current study, we sought to determine whether ILC2 is an important regulator of hepatic ischaemia/reperfusion injury (IRI). Methods: ILC2-deficient mice (ICOS-T or NSG) and genetically modified ILC2s were used to investigate the role of ILC2s in murine hepatic IRI. Interactions between ILC2s and eosinophils or macrophages were studied in coculture. The role of human ILC2s was assessed in an immunocompromised mouse model of hepatic IRI. Results: Administration of IL-33 prevented hepatic IRI in association with reduction of neutrophil infiltration and inflammatory mediators in the liver. IL-33-treated mice had elevated numbers of ILC2s, eosinophils, and regulatory T cells. Eosinophils, but not regulatory T cells, were required for IL-33-mediated hepatoprotection in IRI mice. Depletion of ILC2s substantially abolished the protective effect of IL-33 in hepatic IRI, indicating that ILC2s play critical roles in IL-33-mediated liver protection. Adoptive transfer of ex vivo-expanded ILC2s improved liver function and attenuated histologic damage in mice subjected to IRI. Mechanistic studies combining genetic and adoptive transfer approaches identified a protective role of ILC2s through promoting IL-13-dependent induction of anti-inflammatory macrophages and IL-5-dependent elevation of eosinophils in IRI. Furthermore, in vivo expansion of human ILC2s by IL-33 or transfer of ex vivo-expanded human ILC2s ameliorated hepatic IRI in an immunocompromised mouse model of hepatic IRI. Conclusions: This study provides insight into the mechanisms of ILC2-mediated liver protection that could serve as therapeutic targets to treat acute liver injury. Impact and Implications: We report that type 2 innate lymphoid cells (ILC2s) are important regulators in a mouse model of liver ischaemia/reperfusion injury (IRI). Through manipulation of macrophage and eosinophil phenotypes, ILC2s mitigate liver inflammation and injury during liver IRI. We propose that ILC2s have the potential to serve as a therapeutic tool for protecting against acute liver injury and lay the foundation for translation of ILC2 therapy to human liver disease.http://www.sciencedirect.com/science/article/pii/S2589555923001684Innate lymphoid cellsHepatic ischaemia/reperfusion injuryIL-33EosinophilsMacrophages |
| spellingShingle | Qi Cao Ruifeng Wang Zhiguo Niu Titi Chen Farhana Azmi Scott A. Read Jianwei Chen Vincent W.S. Lee Chunze Zhou Sohel Julovi Qingsong Huang Yuan Min Wang Malcolm R. Starkey Guoping Zheng Stephen I. Alexander Jacob George Yiping Wang David C.H. Harris Type 2 innate lymphoid cells are protective against hepatic ischaemia/reperfusion injury JHEP Reports Innate lymphoid cells Hepatic ischaemia/reperfusion injury IL-33 Eosinophils Macrophages |
| title | Type 2 innate lymphoid cells are protective against hepatic ischaemia/reperfusion injury |
| title_full | Type 2 innate lymphoid cells are protective against hepatic ischaemia/reperfusion injury |
| title_fullStr | Type 2 innate lymphoid cells are protective against hepatic ischaemia/reperfusion injury |
| title_full_unstemmed | Type 2 innate lymphoid cells are protective against hepatic ischaemia/reperfusion injury |
| title_short | Type 2 innate lymphoid cells are protective against hepatic ischaemia/reperfusion injury |
| title_sort | type 2 innate lymphoid cells are protective against hepatic ischaemia reperfusion injury |
| topic | Innate lymphoid cells Hepatic ischaemia/reperfusion injury IL-33 Eosinophils Macrophages |
| url | http://www.sciencedirect.com/science/article/pii/S2589555923001684 |
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