Tim-3 pathway dysregulation and targeting in sepsis-induced immunosuppression
Abstract Sepsis is a major medical problem which causes millions of deaths worldwide every year. The host immune response in sepsis is characterized by acute inflammation and a simultaneous state of immunosuppression. In the later stage of sepsis, immunosuppression is a crucial factor that increases...
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| Format: | Article |
| Language: | English |
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BMC
2024-12-01
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| Series: | European Journal of Medical Research |
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| Online Access: | https://doi.org/10.1186/s40001-024-02203-w |
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| author | Jialiu Luo Cong Zhang Deng Chen Teding Chang Shunyao Chen Zhiqiang Lin Chengla Yi Zhao-Hui Tang |
| author_facet | Jialiu Luo Cong Zhang Deng Chen Teding Chang Shunyao Chen Zhiqiang Lin Chengla Yi Zhao-Hui Tang |
| author_sort | Jialiu Luo |
| collection | DOAJ |
| description | Abstract Sepsis is a major medical problem which causes millions of deaths worldwide every year. The host immune response in sepsis is characterized by acute inflammation and a simultaneous state of immunosuppression. In the later stage of sepsis, immunosuppression is a crucial factor that increases the susceptibility of septic patients to secondary infection and mortality. It is characterized by T cell exhaustion, excessive production of anti-inflammatory cytokines, hyperproliferation of immune suppressor cells and aberrant expression of immune checkpoint molecules. T cell immunoglobulin and mucin domain 3 (Tim-3), an immune checkpoint molecule, is found on the surface of various cells, including macrophages, NK cells, NKT cells, and T cells. There are four different ligands for Tim-3, and accumulating evidence indicates that Tim-3 and its ligands play a crucial role in regulating immune cell dysfunction during sepsis. Anti-Tim-3 antibodies have been applied in the field of cancer immunotherapy and have achieved positive therapeutic effects in some clinical trials. However, the therapeutic efficacy of Tim-3 blockade is still controversial in animal models of sepsis. These challenges highlight the need for a deeper understanding of Tim-3 signaling in sepsis. This review examines the comprehensive effect of Tim-3 signaling in the development of sepsis-induced immunosuppression and the therapeutic efficacy of Tim-3 blockade. |
| format | Article |
| id | doaj-art-7b6f993bc2f444879c93ad5beb8c9003 |
| institution | Kabale University |
| issn | 2047-783X |
| language | English |
| publishDate | 2024-12-01 |
| publisher | BMC |
| record_format | Article |
| series | European Journal of Medical Research |
| spelling | doaj-art-7b6f993bc2f444879c93ad5beb8c90032024-12-22T12:22:27ZengBMCEuropean Journal of Medical Research2047-783X2024-12-0129111310.1186/s40001-024-02203-wTim-3 pathway dysregulation and targeting in sepsis-induced immunosuppressionJialiu Luo0Cong Zhang1Deng Chen2Teding Chang3Shunyao Chen4Zhiqiang Lin5Chengla Yi6Zhao-Hui Tang7Department of Trauma Surgery, Emergency Surgery & Surgical Critical, Tongji Trauma Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Trauma Surgery, Emergency Surgery & Surgical Critical, Tongji Trauma Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Trauma Surgery, Emergency Surgery & Surgical Critical, Tongji Trauma Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Trauma Surgery, Emergency Surgery & Surgical Critical, Tongji Trauma Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Trauma Surgery, Emergency Surgery & Surgical Critical, Tongji Trauma Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Trauma Surgery, Emergency Surgery & Surgical Critical, Tongji Trauma Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Trauma Surgery, Emergency Surgery & Surgical Critical, Tongji Trauma Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Trauma Surgery, Emergency Surgery & Surgical Critical, Tongji Trauma Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyAbstract Sepsis is a major medical problem which causes millions of deaths worldwide every year. The host immune response in sepsis is characterized by acute inflammation and a simultaneous state of immunosuppression. In the later stage of sepsis, immunosuppression is a crucial factor that increases the susceptibility of septic patients to secondary infection and mortality. It is characterized by T cell exhaustion, excessive production of anti-inflammatory cytokines, hyperproliferation of immune suppressor cells and aberrant expression of immune checkpoint molecules. T cell immunoglobulin and mucin domain 3 (Tim-3), an immune checkpoint molecule, is found on the surface of various cells, including macrophages, NK cells, NKT cells, and T cells. There are four different ligands for Tim-3, and accumulating evidence indicates that Tim-3 and its ligands play a crucial role in regulating immune cell dysfunction during sepsis. Anti-Tim-3 antibodies have been applied in the field of cancer immunotherapy and have achieved positive therapeutic effects in some clinical trials. However, the therapeutic efficacy of Tim-3 blockade is still controversial in animal models of sepsis. These challenges highlight the need for a deeper understanding of Tim-3 signaling in sepsis. This review examines the comprehensive effect of Tim-3 signaling in the development of sepsis-induced immunosuppression and the therapeutic efficacy of Tim-3 blockade.https://doi.org/10.1186/s40001-024-02203-wImmune checkpointTim-3SepsisImmunosuppression |
| spellingShingle | Jialiu Luo Cong Zhang Deng Chen Teding Chang Shunyao Chen Zhiqiang Lin Chengla Yi Zhao-Hui Tang Tim-3 pathway dysregulation and targeting in sepsis-induced immunosuppression European Journal of Medical Research Immune checkpoint Tim-3 Sepsis Immunosuppression |
| title | Tim-3 pathway dysregulation and targeting in sepsis-induced immunosuppression |
| title_full | Tim-3 pathway dysregulation and targeting in sepsis-induced immunosuppression |
| title_fullStr | Tim-3 pathway dysregulation and targeting in sepsis-induced immunosuppression |
| title_full_unstemmed | Tim-3 pathway dysregulation and targeting in sepsis-induced immunosuppression |
| title_short | Tim-3 pathway dysregulation and targeting in sepsis-induced immunosuppression |
| title_sort | tim 3 pathway dysregulation and targeting in sepsis induced immunosuppression |
| topic | Immune checkpoint Tim-3 Sepsis Immunosuppression |
| url | https://doi.org/10.1186/s40001-024-02203-w |
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