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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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Autores principales: Zheng, Wenjie, Fan, Xiaorui, Yang, Zhaohui, Shangguan, Yaoyao, Jin, Taijie, Liu, Yan, Huang, Jiqian, Ye, Xiaohua, Zhou, Qing, Li, Xiaozhong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9530813/
https://www.ncbi.nlm.nih.gov/pubmed/36203570
http://dx.doi.org/10.3389/fimmu.2022.926087
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author Zheng, Wenjie
Fan, Xiaorui
Yang, Zhaohui
Shangguan, Yaoyao
Jin, Taijie
Liu, Yan
Huang, Jiqian
Ye, Xiaohua
Zhou, Qing
Li, Xiaozhong
author_facet Zheng, Wenjie
Fan, Xiaorui
Yang, Zhaohui
Shangguan, Yaoyao
Jin, Taijie
Liu, Yan
Huang, Jiqian
Ye, Xiaohua
Zhou, Qing
Li, Xiaozhong
author_sort Zheng, Wenjie
collection PubMed
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.
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spelling pubmed-95308132022-10-05 Strong inflammatory signatures in the neutrophils of PAMI syndrome Zheng, Wenjie Fan, Xiaorui Yang, Zhaohui Shangguan, Yaoyao Jin, Taijie Liu, Yan Huang, Jiqian Ye, Xiaohua Zhou, Qing Li, Xiaozhong Front Immunol Immunology 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. Frontiers Media S.A. 2022-09-20 /pmc/articles/PMC9530813/ /pubmed/36203570 http://dx.doi.org/10.3389/fimmu.2022.926087 Text en Copyright © 2022 Zheng, Fan, Yang, Shangguan, Jin, Liu, Huang, Ye, Zhou and Li https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Zheng, Wenjie
Fan, Xiaorui
Yang, Zhaohui
Shangguan, Yaoyao
Jin, Taijie
Liu, Yan
Huang, Jiqian
Ye, Xiaohua
Zhou, Qing
Li, Xiaozhong
Strong inflammatory signatures in the neutrophils of PAMI syndrome
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 Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9530813/
https://www.ncbi.nlm.nih.gov/pubmed/36203570
http://dx.doi.org/10.3389/fimmu.2022.926087
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