Platelet–Monocyte Aggregate Instigates Inflammation and Vasculopathy in Kawasaki Disease
Abstract Kawasaki disease (KD) is a severe acute febrile illness and systemic vasculitis that causes coronary artery aneurysms in young children. Platelet hyperreactivity and an aberrant immune response are key indicators of KD; however, the mechanism by which hyperactive platelets contribute to inf...
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Wiley
2025-02-01
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| Series: | Advanced Science |
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| Online Access: | https://doi.org/10.1002/advs.202406282 |
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| author | Yuan Zhang Cuiping Jia Manli Guo Qian Chen Ying Wen Ting Wang Yinyin Xie Xuejiao Fan Jingwen Gao Timur O. Yarovinsky Renjing Liu Zhiyong Jiang Mengmeng Wang Jin Zhou Di Che Lanyan Fu Richard Edelson Xiaoqiong Gu John Hwa Wai Ho Tang |
| author_facet | Yuan Zhang Cuiping Jia Manli Guo Qian Chen Ying Wen Ting Wang Yinyin Xie Xuejiao Fan Jingwen Gao Timur O. Yarovinsky Renjing Liu Zhiyong Jiang Mengmeng Wang Jin Zhou Di Che Lanyan Fu Richard Edelson Xiaoqiong Gu John Hwa Wai Ho Tang |
| author_sort | Yuan Zhang |
| collection | DOAJ |
| description | Abstract Kawasaki disease (KD) is a severe acute febrile illness and systemic vasculitis that causes coronary artery aneurysms in young children. Platelet hyperreactivity and an aberrant immune response are key indicators of KD; however, the mechanism by which hyperactive platelets contribute to inflammation and vasculopathy in KD remains unclear. A cytokine‐mediated positive feedback loop between KD platelets and monocytes is identified. KD platelet–monocyte aggregates (MPAs) are mediated by an initial interaction of P‐selectin (cluster of differentiation 62P, CD62p) and its glycoprotein ligand 1 (PSGL‐1). This is followed by a coordinated interaction of platelet glycoprotein (GP)Ibα with monocyte CD11b. Monocyte‐activated platelets initiate transforming growth factor (TGF)β1 release, which results in nuclear localization of nuclear factor kappaB in monocytes, therefore, driving the phenotypic conversion of classical monocytes (CD14+CD16−) into proinflammatory monocytes (CD14+CD16+). The platelet‐activated monocytes release interleukin‐1 and tissue necrotic factor‐α, which promote further platelet activation. KD‐induced inflammation and vasculopathy are prevented by inhibiting the components of this positive feedback loop. Notably, mice deficient in platelet TGFβ1 show less MPA and CD14+CD16+ monocytes, along with reduced inflammation and vasculopathy. These findings reveal that platelet–monocyte interactive proteins (CD62p/PSGL‐1 and (GP)Ibα/CD11b) and cytokine mediators (platelet TGFβ1) are potential biomarkers and therapeutic targets for KD vasculopathy. |
| format | Article |
| id | doaj-art-8976f7b3563246c88334bb182ae4778b |
| institution | Kabale University |
| issn | 2198-3844 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj-art-8976f7b3563246c88334bb182ae4778b2025-02-04T13:14:54ZengWileyAdvanced Science2198-38442025-02-01125n/an/a10.1002/advs.202406282Platelet–Monocyte Aggregate Instigates Inflammation and Vasculopathy in Kawasaki DiseaseYuan Zhang0Cuiping Jia1Manli Guo2Qian Chen3Ying Wen4Ting Wang5Yinyin Xie6Xuejiao Fan7Jingwen Gao8Timur O. Yarovinsky9Renjing Liu10Zhiyong Jiang11Mengmeng Wang12Jin Zhou13Di Che14Lanyan Fu15Richard Edelson16Xiaoqiong Gu17John Hwa18Wai Ho Tang19Institute of Pediatrics Guangzhou Women and Children's Medical Center Guangzhou Medical University Guangzhou 510623 ChinaInstitute of Pediatrics Guangzhou Women and Children's Medical Center Guangzhou Medical University Guangzhou 510623 ChinaInstitute of Pediatrics Guangzhou Women and Children's Medical Center Guangzhou Medical University Guangzhou 510623 ChinaInstitute of Pediatrics Guangzhou Women and Children's Medical Center Guangzhou Medical University Guangzhou 510623 ChinaInstitute of Pediatrics Guangzhou Women and Children's Medical Center Guangzhou Medical University Guangzhou 510623 ChinaInstitute of Pediatrics Guangzhou Women and Children's Medical Center Guangzhou Medical University Guangzhou 510623 ChinaInstitute of Pediatrics Guangzhou Women and Children's Medical Center Guangzhou Medical University Guangzhou 510623 ChinaInstitute of Pediatrics Guangzhou Women and Children's Medical Center Guangzhou Medical University Guangzhou 510623 ChinaInstitute of Pediatrics Guangzhou Women and Children's Medical Center Guangzhou Medical University Guangzhou 510623 ChinaYale Cardiovascular Research Center Section of Cardiovascular Medicine Department of Internal Medicine Yale University School of Medicine New Haven CT 06511 USAVictor Chang Cardiac Research Institute Sydney 2010 AustraliaDepartment of Blood Transfusion Guangzhou Women and Children's Medical Center Guangzhou Medical University Guangzhou 510623 ChinaDepartment of Children's Ophtalmology Guangzhou Women and Children's Medical Center Guangzhou Medical University Guangzhou 510623 ChinaDepartment of Children's Ophtalmology Guangzhou Women and Children's Medical Center Guangzhou Medical University Guangzhou 510623 ChinaDepartment of Biological Specimen Bank Guangzhou Women and Children's Medical Center Guangzhou Medical University Guangzhou 510623 ChinaDepartment of Biological Specimen Bank Guangzhou Women and Children's Medical Center Guangzhou Medical University Guangzhou 510623 ChinaDepartment of Dermatology School of Medicine Yale University New Haven CT 06511 USADepartment of Biological Specimen Bank Guangzhou Women and Children's Medical Center Guangzhou Medical University Guangzhou 510623 ChinaYale Cardiovascular Research Center Section of Cardiovascular Medicine Department of Internal Medicine Yale University School of Medicine New Haven CT 06511 USAInstitute of Pediatrics Guangzhou Women and Children's Medical Center Guangzhou Medical University Guangzhou 510623 ChinaAbstract Kawasaki disease (KD) is a severe acute febrile illness and systemic vasculitis that causes coronary artery aneurysms in young children. Platelet hyperreactivity and an aberrant immune response are key indicators of KD; however, the mechanism by which hyperactive platelets contribute to inflammation and vasculopathy in KD remains unclear. A cytokine‐mediated positive feedback loop between KD platelets and monocytes is identified. KD platelet–monocyte aggregates (MPAs) are mediated by an initial interaction of P‐selectin (cluster of differentiation 62P, CD62p) and its glycoprotein ligand 1 (PSGL‐1). This is followed by a coordinated interaction of platelet glycoprotein (GP)Ibα with monocyte CD11b. Monocyte‐activated platelets initiate transforming growth factor (TGF)β1 release, which results in nuclear localization of nuclear factor kappaB in monocytes, therefore, driving the phenotypic conversion of classical monocytes (CD14+CD16−) into proinflammatory monocytes (CD14+CD16+). The platelet‐activated monocytes release interleukin‐1 and tissue necrotic factor‐α, which promote further platelet activation. KD‐induced inflammation and vasculopathy are prevented by inhibiting the components of this positive feedback loop. Notably, mice deficient in platelet TGFβ1 show less MPA and CD14+CD16+ monocytes, along with reduced inflammation and vasculopathy. These findings reveal that platelet–monocyte interactive proteins (CD62p/PSGL‐1 and (GP)Ibα/CD11b) and cytokine mediators (platelet TGFβ1) are potential biomarkers and therapeutic targets for KD vasculopathy.https://doi.org/10.1002/advs.202406282inflammationKawasaki diseasemonocyteplateletvasculopathy |
| spellingShingle | Yuan Zhang Cuiping Jia Manli Guo Qian Chen Ying Wen Ting Wang Yinyin Xie Xuejiao Fan Jingwen Gao Timur O. Yarovinsky Renjing Liu Zhiyong Jiang Mengmeng Wang Jin Zhou Di Che Lanyan Fu Richard Edelson Xiaoqiong Gu John Hwa Wai Ho Tang Platelet–Monocyte Aggregate Instigates Inflammation and Vasculopathy in Kawasaki Disease Advanced Science inflammation Kawasaki disease monocyte platelet vasculopathy |
| title | Platelet–Monocyte Aggregate Instigates Inflammation and Vasculopathy in Kawasaki Disease |
| title_full | Platelet–Monocyte Aggregate Instigates Inflammation and Vasculopathy in Kawasaki Disease |
| title_fullStr | Platelet–Monocyte Aggregate Instigates Inflammation and Vasculopathy in Kawasaki Disease |
| title_full_unstemmed | Platelet–Monocyte Aggregate Instigates Inflammation and Vasculopathy in Kawasaki Disease |
| title_short | Platelet–Monocyte Aggregate Instigates Inflammation and Vasculopathy in Kawasaki Disease |
| title_sort | platelet monocyte aggregate instigates inflammation and vasculopathy in kawasaki disease |
| topic | inflammation Kawasaki disease monocyte platelet vasculopathy |
| url | https://doi.org/10.1002/advs.202406282 |
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