Strong inflammatory signatures in the neutrophils of PAMI syndrome
PSTPIP1 (proline-serine-threonine phosphatase-interactive protein 1)–associated myeloid-related proteinemia inflammatory (PAMI) syndrome is a rare autoinflammatory disease caused by heterozygous gain-of-function mutation in PSTPIP1. As one of the PSTPIP1-associated inflammatory diseases (PAIDs), neu...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-09-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.926087/full |
| _version_ | 1798035759485157376 |
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| author | Wenjie Zheng Wenjie Zheng Xiaorui Fan Zhaohui Yang Yaoyao Shangguan Taijie Jin Yan Liu Jiqian Huang Xiaohua Ye Qing Zhou Xiaozhong Li |
| author_facet | Wenjie Zheng Wenjie Zheng Xiaorui Fan Zhaohui Yang Yaoyao Shangguan Taijie Jin Yan Liu Jiqian Huang Xiaohua Ye Qing Zhou Xiaozhong Li |
| author_sort | Wenjie Zheng |
| collection | DOAJ |
| description | PSTPIP1 (proline-serine-threonine phosphatase-interactive protein 1)–associated myeloid-related proteinemia inflammatory (PAMI) syndrome is a rare autoinflammatory disease caused by heterozygous gain-of-function mutation in PSTPIP1. As one of the PSTPIP1-associated inflammatory diseases (PAIDs), neutropenia is a distinct manifestation to separate PAMI syndrome from other PAIDs. This study aimed to investigate the potential role of neutrophils and inflammatory signatures in the pathogenesis of PAMI. PAMI neutrophils displayed markedly increased production of interleukin-1β (IL-1β) and IL-18 by enzyme linked immunosorbent assay (ELISA) assay and intracellular cytokine staining. ASC speck formation and lactic dehydrogenase (LDH) release are also increased in patient neutrophils suggesting elevated pyrin inflammasome activation followed by upregulated cell death in PAMI neutrophils. RNA sequencing result showed strong inflammatory signals in both nuclear-factor kappa B (NF-κB) pathway and interferon (IFN) pathway in patient neutrophils. This study highlighted that elevated proinflammatory cytokines IL-1β and IL-18, increased pyrin inflammasome activation, and upregulation of NF-κB and IFN signaling pathways in neutrophils play important roles in pathogenicity of PAMI syndrome. |
| first_indexed | 2024-04-11T21:02:41Z |
| format | Article |
| id | doaj.art-22b82c4093c8478e9063d9b9f50cda7f |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-11T21:02:41Z |
| publishDate | 2022-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-22b82c4093c8478e9063d9b9f50cda7f2022-12-22T04:03:27ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-09-011310.3389/fimmu.2022.926087926087Strong inflammatory signatures in the neutrophils of PAMI syndromeWenjie Zheng0Wenjie Zheng1Xiaorui Fan2Zhaohui Yang3Yaoyao Shangguan4Taijie Jin5Yan Liu6Jiqian Huang7Xiaohua Ye8Qing Zhou9Xiaozhong Li10Department of Nephrology and Immunology, Children’s Hospital of Soochow University, Suzhou, ChinaDepartment of Pediatric Rheumatology, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, ChinaLife Sciences Institute, Zhejiang University, Hangzhou, ChinaLife Sciences Institute, Zhejiang University, Hangzhou, ChinaDepartment of Pediatric Rheumatology, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, ChinaLife Sciences Institute, Zhejiang University, Hangzhou, ChinaDepartment of Rheumotology, Dalian Municipal Women and Children’s Medical Center, Dalian, ChinaDepartment of Pediatric Rheumatology, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, ChinaDepartment of Pediatric Rheumatology, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, ChinaLife Sciences Institute, Zhejiang University, Hangzhou, ChinaDepartment of Nephrology and Immunology, Children’s Hospital of Soochow University, Suzhou, ChinaPSTPIP1 (proline-serine-threonine phosphatase-interactive protein 1)–associated myeloid-related proteinemia inflammatory (PAMI) syndrome is a rare autoinflammatory disease caused by heterozygous gain-of-function mutation in PSTPIP1. As one of the PSTPIP1-associated inflammatory diseases (PAIDs), neutropenia is a distinct manifestation to separate PAMI syndrome from other PAIDs. This study aimed to investigate the potential role of neutrophils and inflammatory signatures in the pathogenesis of PAMI. PAMI neutrophils displayed markedly increased production of interleukin-1β (IL-1β) and IL-18 by enzyme linked immunosorbent assay (ELISA) assay and intracellular cytokine staining. ASC speck formation and lactic dehydrogenase (LDH) release are also increased in patient neutrophils suggesting elevated pyrin inflammasome activation followed by upregulated cell death in PAMI neutrophils. RNA sequencing result showed strong inflammatory signals in both nuclear-factor kappa B (NF-κB) pathway and interferon (IFN) pathway in patient neutrophils. This study highlighted that elevated proinflammatory cytokines IL-1β and IL-18, increased pyrin inflammasome activation, and upregulation of NF-κB and IFN signaling pathways in neutrophils play important roles in pathogenicity of PAMI syndrome.https://www.frontiersin.org/articles/10.3389/fimmu.2022.926087/fullinflammationneutrophilPAMI syndromePSTPIP1pyrin inflammasome |
| spellingShingle | Wenjie Zheng Wenjie Zheng Xiaorui Fan Zhaohui Yang Yaoyao Shangguan Taijie Jin Yan Liu Jiqian Huang Xiaohua Ye Qing Zhou Xiaozhong Li Strong inflammatory signatures in the neutrophils of PAMI syndrome Frontiers in Immunology inflammation neutrophil PAMI syndrome PSTPIP1 pyrin inflammasome |
| title | Strong inflammatory signatures in the neutrophils of PAMI syndrome |
| title_full | Strong inflammatory signatures in the neutrophils of PAMI syndrome |
| title_fullStr | Strong inflammatory signatures in the neutrophils of PAMI syndrome |
| title_full_unstemmed | Strong inflammatory signatures in the neutrophils of PAMI syndrome |
| title_short | Strong inflammatory signatures in the neutrophils of PAMI syndrome |
| title_sort | strong inflammatory signatures in the neutrophils of pami syndrome |
| topic | inflammation neutrophil PAMI syndrome PSTPIP1 pyrin inflammasome |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.926087/full |
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