Activated Immune and Complement C3 Are Potential Contributors in MASH via Stimulating Neutrophil Extracellular Traps
The number of metabolic dysfunction-associated steatotic liver disease (MASLD) patients is increasing rapidly. More attention has been paid to the relationship between immunity and MASLD. This study explored the roles of serum autoantibodies, immunoglobulins, and complements in MASLD. A total of 182...
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MDPI AG
2025-05-01
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| author | Ao Liu Xiaoling Deng Shuhui Hou Yuwen Xi Keshu Xu |
| author_facet | Ao Liu Xiaoling Deng Shuhui Hou Yuwen Xi Keshu Xu |
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| description | The number of metabolic dysfunction-associated steatotic liver disease (MASLD) patients is increasing rapidly. More attention has been paid to the relationship between immunity and MASLD. This study explored the roles of serum autoantibodies, immunoglobulins, and complements in MASLD. A total of 182 MASLD patients were investigated and grouped by autoantibody or NAS scores. Correlation between immunology and clinical features was assessed. In addition, metabolic dysfunction-associated steatohepatitis (MASH) models were constructed to verify the findings. Neutrophils were isolated from mice and treated with complement C3 to investigate the association between C3 and neutrophil extracellular traps (NETs). IgG, IgM, and NAS scores in the autoantibody positive group were significantly higher than those in the autoantibody negative group. Antinuclear antibodies (ANA), IgA, IgE, IgG, C3, C4, ALT, and AST were related to MASH. Meanwhile, IgA and C3 correlated with the severity of MASLD. The ROC curve showed that IgA > 2.990 g/L or C3 > 1.115 g/L predicted the presence of MASH. More importantly, IgG, activated C3, and NETs were increased in MASH. C3 stimulation directly induced NET formation in the neutrophils. Immunity systems were activated in MASH and elevated IgG activated C3 to stimulate the production of NETs, thus exacerbating MASH. |
| format | Article |
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| language | English |
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| spelling | doaj-art-3d59b18c83b542b8b9dc74fe62cf0a112025-08-20T01:56:14ZengMDPI AGCells2073-44092025-05-01141074010.3390/cells14100740Activated Immune and Complement C3 Are Potential Contributors in MASH via Stimulating Neutrophil Extracellular TrapsAo Liu0Xiaoling Deng1Shuhui Hou2Yuwen Xi3Keshu Xu4Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan 430022, ChinaDivision of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan 430022, ChinaDivision of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan 430022, ChinaDivision of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan 430022, ChinaDivision of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan 430022, ChinaThe number of metabolic dysfunction-associated steatotic liver disease (MASLD) patients is increasing rapidly. More attention has been paid to the relationship between immunity and MASLD. This study explored the roles of serum autoantibodies, immunoglobulins, and complements in MASLD. A total of 182 MASLD patients were investigated and grouped by autoantibody or NAS scores. Correlation between immunology and clinical features was assessed. In addition, metabolic dysfunction-associated steatohepatitis (MASH) models were constructed to verify the findings. Neutrophils were isolated from mice and treated with complement C3 to investigate the association between C3 and neutrophil extracellular traps (NETs). IgG, IgM, and NAS scores in the autoantibody positive group were significantly higher than those in the autoantibody negative group. Antinuclear antibodies (ANA), IgA, IgE, IgG, C3, C4, ALT, and AST were related to MASH. Meanwhile, IgA and C3 correlated with the severity of MASLD. The ROC curve showed that IgA > 2.990 g/L or C3 > 1.115 g/L predicted the presence of MASH. More importantly, IgG, activated C3, and NETs were increased in MASH. C3 stimulation directly induced NET formation in the neutrophils. Immunity systems were activated in MASH and elevated IgG activated C3 to stimulate the production of NETs, thus exacerbating MASH.https://www.mdpi.com/2073-4409/14/10/740metabolic dysfunction-associated steatotic liver diseasecomplement C3neutrophil extracellular trapimmunoglobulinautoantibody |
| spellingShingle | Ao Liu Xiaoling Deng Shuhui Hou Yuwen Xi Keshu Xu Activated Immune and Complement C3 Are Potential Contributors in MASH via Stimulating Neutrophil Extracellular Traps Cells metabolic dysfunction-associated steatotic liver disease complement C3 neutrophil extracellular trap immunoglobulin autoantibody |
| title | Activated Immune and Complement C3 Are Potential Contributors in MASH via Stimulating Neutrophil Extracellular Traps |
| title_full | Activated Immune and Complement C3 Are Potential Contributors in MASH via Stimulating Neutrophil Extracellular Traps |
| title_fullStr | Activated Immune and Complement C3 Are Potential Contributors in MASH via Stimulating Neutrophil Extracellular Traps |
| title_full_unstemmed | Activated Immune and Complement C3 Are Potential Contributors in MASH via Stimulating Neutrophil Extracellular Traps |
| title_short | Activated Immune and Complement C3 Are Potential Contributors in MASH via Stimulating Neutrophil Extracellular Traps |
| title_sort | activated immune and complement c3 are potential contributors in mash via stimulating neutrophil extracellular traps |
| topic | metabolic dysfunction-associated steatotic liver disease complement C3 neutrophil extracellular trap immunoglobulin autoantibody |
| url | https://www.mdpi.com/2073-4409/14/10/740 |
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