Enhancement of CD8+T cell cytotoxicity activity by IFN-α implies alternative pathologic role in systemic lupus erythematosus
Objective: Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease which is affected by the environmental, genetic factors as well as the immune system. Previous reports have implicated IFN-α in the pathogenesis of SLE. Up to date, however, no research has ever investigated the effe...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-06-01
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| Series: | Journal of Translational Autoimmunity |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589909025000115 |
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| author | Chen-xing Zhang You-ying Mao Yu-pin Tan Mei-yu Zhang Kang Shao Shu-jun Wang Ping Ji Jia-yuan Wang Lei Yin Ying Wang |
| author_facet | Chen-xing Zhang You-ying Mao Yu-pin Tan Mei-yu Zhang Kang Shao Shu-jun Wang Ping Ji Jia-yuan Wang Lei Yin Ying Wang |
| author_sort | Chen-xing Zhang |
| collection | DOAJ |
| description | Objective: Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease which is affected by the environmental, genetic factors as well as the immune system. Previous reports have implicated IFN-α in the pathogenesis of SLE. Up to date, however, no research has ever investigated the effect of IFN-α on CD8+T cells, which might be implicated in the pathogenesis of SLE. In the present study, we aimed to explore the pathologic role of IFN-α in regard to dysfunction of CD8+T cells in SLE. Methods: Serum level of IFN-α was detected in SLE and healthy controls (HC). Surface expression of lysosome-associated membrane protein 1 (LAMP-1; CD107a) and secretion of granzyme B of CD8+T cells was measured in SLE and HC with or without IFN-α co-stimulation/PI3K inhibitor. Results: Our results demonstrated that there was increased surface expression of CD107a of CD8+T cells in SLE patients compared with healthy controls (HC), indicating enhanced cytotoxicity of CD8+T cells in SLE patients. Meanwhile, increased secretion of granzyme B was also detected in CD8+T cells of SLE compared with HC, which correlated with the disease activity (SLEDAI). Furthermore, elevated serum level of IFN-α in SLE was confirmed in our study. In vitro study, granzyme B secretion by CD8+T cells was upregulated upon IFN-α costimulation, which was consistent with enhanced cytotoxicity of CD8+T cells upon IFN-α costimulation, as reflected by elevated surface expression of CD107a. PI3K inhibitor reversed increased granzyme B synthesis upon IFN-α costimulation in a dose-dependent manner. Conclusion: In summary, elevated serum level of IFN-α was responsible for increased secretion of granzyme B and enhanced cytotoxicity of CD8+T cells in SLE and this process may be related to PI3K pathway. Relevant molecules and mechanism remains to be explored in the future. |
| format | Article |
| id | doaj-art-b963bfb0a1b540beb0462ce5d4cec3ce |
| institution | Kabale University |
| issn | 2589-9090 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Translational Autoimmunity |
| spelling | doaj-art-b963bfb0a1b540beb0462ce5d4cec3ce2025-02-10T04:34:45ZengElsevierJournal of Translational Autoimmunity2589-90902025-06-0110100276Enhancement of CD8+T cell cytotoxicity activity by IFN-α implies alternative pathologic role in systemic lupus erythematosusChen-xing Zhang0You-ying Mao1Yu-pin Tan2Mei-yu Zhang3Kang Shao4Shu-jun Wang5Ping Ji6Jia-yuan Wang7Lei Yin8Ying Wang9Department of Nephrology, Shanghai Children's Medical Center, Shanghai Jiaotong University School of Medicine, Shanghai, 200127, ChinaDepartment of Nephrology, Shanghai Children's Medical Center, Shanghai Jiaotong University School of Medicine, Shanghai, 200127, China; Department of Pediatrics, Songjiang Hospital Affiliated to the Shanghai Jiaotong University School of Medicine, Shanghai, ChinaDepartment of Pediatrics, Hunan Provincial People's Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha, 410005, ChinaShanghai Institute of Immunology, Shanghai Jiaotong University School of Medicine, Shanghai, 200127, ChinaDepartment of Laboratory, Renji Hospital affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, 200127, ChinaShanghai Institute of Immunology, Shanghai Jiaotong University School of Medicine, Shanghai, 200127, ChinaShanghai Institute of Immunology, Shanghai Jiaotong University School of Medicine, Shanghai, 200127, ChinaDepartment of Laboratory, Renji Hospital affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, 200127, ChinaDepartment of Nephrology, Shanghai Children's Medical Center, Shanghai Jiaotong University School of Medicine, Shanghai, 200127, China; Corresponding author.Shanghai Institute of Immunology, Shanghai Jiaotong University School of Medicine, Shanghai, 200127, China; Corresponding author.Objective: Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease which is affected by the environmental, genetic factors as well as the immune system. Previous reports have implicated IFN-α in the pathogenesis of SLE. Up to date, however, no research has ever investigated the effect of IFN-α on CD8+T cells, which might be implicated in the pathogenesis of SLE. In the present study, we aimed to explore the pathologic role of IFN-α in regard to dysfunction of CD8+T cells in SLE. Methods: Serum level of IFN-α was detected in SLE and healthy controls (HC). Surface expression of lysosome-associated membrane protein 1 (LAMP-1; CD107a) and secretion of granzyme B of CD8+T cells was measured in SLE and HC with or without IFN-α co-stimulation/PI3K inhibitor. Results: Our results demonstrated that there was increased surface expression of CD107a of CD8+T cells in SLE patients compared with healthy controls (HC), indicating enhanced cytotoxicity of CD8+T cells in SLE patients. Meanwhile, increased secretion of granzyme B was also detected in CD8+T cells of SLE compared with HC, which correlated with the disease activity (SLEDAI). Furthermore, elevated serum level of IFN-α in SLE was confirmed in our study. In vitro study, granzyme B secretion by CD8+T cells was upregulated upon IFN-α costimulation, which was consistent with enhanced cytotoxicity of CD8+T cells upon IFN-α costimulation, as reflected by elevated surface expression of CD107a. PI3K inhibitor reversed increased granzyme B synthesis upon IFN-α costimulation in a dose-dependent manner. Conclusion: In summary, elevated serum level of IFN-α was responsible for increased secretion of granzyme B and enhanced cytotoxicity of CD8+T cells in SLE and this process may be related to PI3K pathway. Relevant molecules and mechanism remains to be explored in the future.http://www.sciencedirect.com/science/article/pii/S2589909025000115Systemic lupus erythematosus (SLE)Lupus nephritis (LN)Granzyme BCytotoxicityPI3K |
| spellingShingle | Chen-xing Zhang You-ying Mao Yu-pin Tan Mei-yu Zhang Kang Shao Shu-jun Wang Ping Ji Jia-yuan Wang Lei Yin Ying Wang Enhancement of CD8+T cell cytotoxicity activity by IFN-α implies alternative pathologic role in systemic lupus erythematosus Journal of Translational Autoimmunity Systemic lupus erythematosus (SLE) Lupus nephritis (LN) Granzyme B Cytotoxicity PI3K |
| title | Enhancement of CD8+T cell cytotoxicity activity by IFN-α implies alternative pathologic role in systemic lupus erythematosus |
| title_full | Enhancement of CD8+T cell cytotoxicity activity by IFN-α implies alternative pathologic role in systemic lupus erythematosus |
| title_fullStr | Enhancement of CD8+T cell cytotoxicity activity by IFN-α implies alternative pathologic role in systemic lupus erythematosus |
| title_full_unstemmed | Enhancement of CD8+T cell cytotoxicity activity by IFN-α implies alternative pathologic role in systemic lupus erythematosus |
| title_short | Enhancement of CD8+T cell cytotoxicity activity by IFN-α implies alternative pathologic role in systemic lupus erythematosus |
| title_sort | enhancement of cd8 t cell cytotoxicity activity by ifn α implies alternative pathologic role in systemic lupus erythematosus |
| topic | Systemic lupus erythematosus (SLE) Lupus nephritis (LN) Granzyme B Cytotoxicity PI3K |
| url | http://www.sciencedirect.com/science/article/pii/S2589909025000115 |
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