Immune signatures of megakaryocytes in persistent inflammation-immunosuppression and catabolism syndrome
Persistent inflammation-immunosuppression and catabolism syndrome (PICS) is a severe condition that may follow sepsis and is characterized by ongoing inflammation and immune suppression, diminishing quality of life and potentially causing death. The role of megakaryocytes (MKs) in PICS, despite thei...
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China Science Publishing & Media Ltd.
2025-05-01
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| Series: | Acta Biochimica et Biophysica Sinica |
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| Online Access: | https://www.sciengine.com/doi/10.3724/abbs.2025087 |
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| author | Sun Xingfeng Nan Ke Zhong Ziwen Liu Zhiqiang Miao Changhong |
| author_facet | Sun Xingfeng Nan Ke Zhong Ziwen Liu Zhiqiang Miao Changhong |
| author_sort | Sun Xingfeng |
| collection | DOAJ |
| description | Persistent inflammation-immunosuppression and catabolism syndrome (PICS) is a severe condition that may follow sepsis and is characterized by ongoing inflammation and immune suppression, diminishing quality of life and potentially causing death. The role of megakaryocytes (MKs) in PICS, despite their association with thrombopoiesis, is not well understood. In this study, we use single-cell RNA sequencing to profile MKs in peripheral blood mononuclear cell samples obtained from 11 patients, including six with PICS, five with sepsis, and five healthy controls, to determine the diversity and molecular signatures of the MKs. Five subgroups of MKs are identified (MK1–MK5), and their proportions vary across the groups. MK1 and MK2 are predominant in PICS. Gene Ontology analysis shows that genes related to antigen processing and presentation and IL-17 signaling are enriched in MK1, whereas genes associated with platelet degranulation and neutrophil activation are enriched in MK2. Moreover, the expression level of CCL5 is markedly increased in MKs. Ligand-receptor analysis reveals dynamic interactions among MKs and T cells, B cells, natural killer cells, monocytes, and macrophages, suggesting a broad role of MKs in immune homeostasis. In PICS model mice, MKs regulate systemic inflammation by reducing the levels of the proinflammatory cytokines TNF-α and IL-17A and promoting lung tissue repair. Our findings establish MKs as essential components of the immune system in PICS and provide new insights into their potential as therapeutic targets for post-sepsis immune dysfunction. |
| format | Article |
| id | doaj-art-453af502e7eb4e29b7f32f8a54089271 |
| institution | DOAJ |
| issn | 1672-9145 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | China Science Publishing & Media Ltd. |
| record_format | Article |
| series | Acta Biochimica et Biophysica Sinica |
| spelling | doaj-art-453af502e7eb4e29b7f32f8a540892712025-08-20T03:07:25ZengChina Science Publishing & Media Ltd.Acta Biochimica et Biophysica Sinica1672-91452025-05-01571325133710.3724/abbs.202508720d259ccImmune signatures of megakaryocytes in persistent inflammation-immunosuppression and catabolism syndromeSun Xingfeng0Nan Ke1Zhong Ziwen2Liu Zhiqiang3Miao Changhong4["Department of Anesthesiology, Zhongshan Hospital, Fudan University, Shanghai 200032, China","Department of Anesthesiology, Obstetrics and Gynecology Hospital of Fudan University, Shanghai 200090, China"]["Department of Anesthesiology, Zhongshan Hospital, Fudan University, Shanghai 200032, China"]["Department of Anesthesiology, Zhongshan Hospital, Fudan University, Shanghai 200032, China"]["Department of Anesthesiology, Obstetrics and Gynecology Hospital of Fudan University, Shanghai 200090, China"]["Department of Anesthesiology, Zhongshan Hospital, Fudan University, Shanghai 200032, China"]Persistent inflammation-immunosuppression and catabolism syndrome (PICS) is a severe condition that may follow sepsis and is characterized by ongoing inflammation and immune suppression, diminishing quality of life and potentially causing death. The role of megakaryocytes (MKs) in PICS, despite their association with thrombopoiesis, is not well understood. In this study, we use single-cell RNA sequencing to profile MKs in peripheral blood mononuclear cell samples obtained from 11 patients, including six with PICS, five with sepsis, and five healthy controls, to determine the diversity and molecular signatures of the MKs. Five subgroups of MKs are identified (MK1–MK5), and their proportions vary across the groups. MK1 and MK2 are predominant in PICS. Gene Ontology analysis shows that genes related to antigen processing and presentation and IL-17 signaling are enriched in MK1, whereas genes associated with platelet degranulation and neutrophil activation are enriched in MK2. Moreover, the expression level of CCL5 is markedly increased in MKs. Ligand-receptor analysis reveals dynamic interactions among MKs and T cells, B cells, natural killer cells, monocytes, and macrophages, suggesting a broad role of MKs in immune homeostasis. In PICS model mice, MKs regulate systemic inflammation by reducing the levels of the proinflammatory cytokines TNF-α and IL-17A and promoting lung tissue repair. Our findings establish MKs as essential components of the immune system in PICS and provide new insights into their potential as therapeutic targets for post-sepsis immune dysfunction.https://www.sciengine.com/doi/10.3724/abbs.2025087persistent inflammation-immunosuppression and catabolism syndromesepsismegakaryocyteimmunesingle-cell RNA sequencing |
| spellingShingle | Sun Xingfeng Nan Ke Zhong Ziwen Liu Zhiqiang Miao Changhong Immune signatures of megakaryocytes in persistent inflammation-immunosuppression and catabolism syndrome Acta Biochimica et Biophysica Sinica persistent inflammation-immunosuppression and catabolism syndrome sepsis megakaryocyte immune single-cell RNA sequencing |
| title | Immune signatures of megakaryocytes in persistent inflammation-immunosuppression and catabolism syndrome |
| title_full | Immune signatures of megakaryocytes in persistent inflammation-immunosuppression and catabolism syndrome |
| title_fullStr | Immune signatures of megakaryocytes in persistent inflammation-immunosuppression and catabolism syndrome |
| title_full_unstemmed | Immune signatures of megakaryocytes in persistent inflammation-immunosuppression and catabolism syndrome |
| title_short | Immune signatures of megakaryocytes in persistent inflammation-immunosuppression and catabolism syndrome |
| title_sort | immune signatures of megakaryocytes in persistent inflammation immunosuppression and catabolism syndrome |
| topic | persistent inflammation-immunosuppression and catabolism syndrome sepsis megakaryocyte immune single-cell RNA sequencing |
| url | https://www.sciengine.com/doi/10.3724/abbs.2025087 |
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