儿童多系统炎症综合征中的 NK 细胞和单核细胞功能障碍

IF 3.6 3区 医学 Q2 IMMUNOLOGY Journal of immunology Pub Date : 2024-11-15 DOI:10.4049/jimmunol.2400395
Jenna K Dick, Jules A Sangala, Venkatramana D Krishna, Aaron Khaimraj, Lydia Hamel, Spencer M Erickson, Dustin Hicks, Yvette Soigner, Laura E Covill, Alexander K Johnson, Michael J Ehrhardt, Keenan Ernste, Petter Brodin, Richard A Koup, Alka Khaitan, Carly Baehr, Beth K Thielen, Christine M Henzler, Caleb Skipper, Jeffrey S Miller, Yenan T Bryceson, Jianming Wu, Chandy C John, Angela Panoskaltsis-Mortari, Alberto Orioles, Marie E Steiner, Maxim C J Cheeran, Marco Pravetoni, Geoffrey T Hart
{"title":"儿童多系统炎症综合征中的 NK 细胞和单核细胞功能障碍","authors":"Jenna K Dick, Jules A Sangala, Venkatramana D Krishna, Aaron Khaimraj, Lydia Hamel, Spencer M Erickson, Dustin Hicks, Yvette Soigner, Laura E Covill, Alexander K Johnson, Michael J Ehrhardt, Keenan Ernste, Petter Brodin, Richard A Koup, Alka Khaitan, Carly Baehr, Beth K Thielen, Christine M Henzler, Caleb Skipper, Jeffrey S Miller, Yenan T Bryceson, Jianming Wu, Chandy C John, Angela Panoskaltsis-Mortari, Alberto Orioles, Marie E Steiner, Maxim C J Cheeran, Marco Pravetoni, Geoffrey T Hart","doi":"10.4049/jimmunol.2400395","DOIUrl":null,"url":null,"abstract":"<p><p>Multisystem inflammatory syndrome in children (MIS-C) is a severe complication of SARS-CoV-2 infection characterized by multiorgan involvement and inflammation. Testing of cellular function ex vivo to understand the aberrant immune response in MIS-C is limited. Despite strong Ab production in MIS-C, SARS-CoV-2 nucleic acid testing can remain positive for 4-6 wk postinfection. Therefore, we hypothesized that dysfunctional cell-mediated Ab responses downstream of Ab production may be responsible for delayed clearance of viral products in MIS-C. In MIS-C, monocytes were hyperfunctional for phagocytosis and cytokine production, whereas NK cells were hypofunctional for both killing and cytokine production. The decreased NK cell cytotoxicity correlated with an NK exhaustion marker signature and systemic IL-6 levels. Potentially providing a therapeutic option, cellular engagers of CD16 and SARS-CoV-2 proteins were found to rescue NK cell function in vitro. Taken together, our results reveal dysregulation in Ab-mediated cellular responses of myeloid and NK cells that likely contribute to the immune pathology of this disease.</p>","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":" ","pages":"1452-1466"},"PeriodicalIF":3.6000,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11533154/pdf/","citationCount":"0","resultStr":"{\"title\":\"NK Cell and Monocyte Dysfunction in Multisystem Inflammatory Syndrome in Children.\",\"authors\":\"Jenna K Dick, Jules A Sangala, Venkatramana D Krishna, Aaron Khaimraj, Lydia Hamel, Spencer M Erickson, Dustin Hicks, Yvette Soigner, Laura E Covill, Alexander K Johnson, Michael J Ehrhardt, Keenan Ernste, Petter Brodin, Richard A Koup, Alka Khaitan, Carly Baehr, Beth K Thielen, Christine M Henzler, Caleb Skipper, Jeffrey S Miller, Yenan T Bryceson, Jianming Wu, Chandy C John, Angela Panoskaltsis-Mortari, Alberto Orioles, Marie E Steiner, Maxim C J Cheeran, Marco Pravetoni, Geoffrey T Hart\",\"doi\":\"10.4049/jimmunol.2400395\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Multisystem inflammatory syndrome in children (MIS-C) is a severe complication of SARS-CoV-2 infection characterized by multiorgan involvement and inflammation. Testing of cellular function ex vivo to understand the aberrant immune response in MIS-C is limited. Despite strong Ab production in MIS-C, SARS-CoV-2 nucleic acid testing can remain positive for 4-6 wk postinfection. Therefore, we hypothesized that dysfunctional cell-mediated Ab responses downstream of Ab production may be responsible for delayed clearance of viral products in MIS-C. In MIS-C, monocytes were hyperfunctional for phagocytosis and cytokine production, whereas NK cells were hypofunctional for both killing and cytokine production. The decreased NK cell cytotoxicity correlated with an NK exhaustion marker signature and systemic IL-6 levels. Potentially providing a therapeutic option, cellular engagers of CD16 and SARS-CoV-2 proteins were found to rescue NK cell function in vitro. Taken together, our results reveal dysregulation in Ab-mediated cellular responses of myeloid and NK cells that likely contribute to the immune pathology of this disease.</p>\",\"PeriodicalId\":16045,\"journal\":{\"name\":\"Journal of immunology\",\"volume\":\" \",\"pages\":\"1452-1466\"},\"PeriodicalIF\":3.6000,\"publicationDate\":\"2024-11-15\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11533154/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of immunology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.4049/jimmunol.2400395\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"IMMUNOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of immunology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.4049/jimmunol.2400395","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
引用次数: 0

摘要

儿童多系统炎症综合征(MIS-C)是 SARS-CoV-2 感染的一种严重并发症,以多器官受累和炎症为特征。为了解 MIS-C 中异常免疫反应而进行的体内外细胞功能测试非常有限。尽管 MIS-C 中会产生大量抗体,但在感染后 4-6 周内,SARS-CoV-2 核酸检测仍可保持阳性。因此,我们推测,Ab产生下游的细胞介导的Ab反应失调可能是MIS-C中病毒产物清除延迟的原因。在 MIS-C 中,单核细胞的吞噬功能和细胞因子产生功能都很强,而 NK 细胞的杀伤功能和细胞因子产生功能都很弱。NK 细胞细胞毒性的降低与 NK 衰竭标记特征和全身 IL-6 水平相关。研究发现,CD16和SARS-CoV-2蛋白的细胞啮合剂可在体外挽救NK细胞的功能,这有可能提供一种治疗选择。总之,我们的研究结果揭示了 Ab 介导的骨髓细胞和 NK 细胞反应失调,这可能是导致该疾病免疫病理学的原因之一。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
NK Cell and Monocyte Dysfunction in Multisystem Inflammatory Syndrome in Children.

Multisystem inflammatory syndrome in children (MIS-C) is a severe complication of SARS-CoV-2 infection characterized by multiorgan involvement and inflammation. Testing of cellular function ex vivo to understand the aberrant immune response in MIS-C is limited. Despite strong Ab production in MIS-C, SARS-CoV-2 nucleic acid testing can remain positive for 4-6 wk postinfection. Therefore, we hypothesized that dysfunctional cell-mediated Ab responses downstream of Ab production may be responsible for delayed clearance of viral products in MIS-C. In MIS-C, monocytes were hyperfunctional for phagocytosis and cytokine production, whereas NK cells were hypofunctional for both killing and cytokine production. The decreased NK cell cytotoxicity correlated with an NK exhaustion marker signature and systemic IL-6 levels. Potentially providing a therapeutic option, cellular engagers of CD16 and SARS-CoV-2 proteins were found to rescue NK cell function in vitro. Taken together, our results reveal dysregulation in Ab-mediated cellular responses of myeloid and NK cells that likely contribute to the immune pathology of this disease.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
Journal of immunology
Journal of immunology 医学-免疫学
CiteScore
8.20
自引率
2.30%
发文量
495
审稿时长
1 months
期刊介绍: The JI publishes novel, peer-reviewed findings in all areas of experimental immunology, including innate and adaptive immunity, inflammation, host defense, clinical immunology, autoimmunity and more. Special sections include Cutting Edge articles, Brief Reviews and Pillars of Immunology. The JI is published by The American Association of Immunologists (AAI)
期刊最新文献
Identification of a Specific Granular Marker of Zebrafish Eosinophils Enables Development of New Tools for Their Study. IL-33 Increases the Magnitude of the Tissue-Resident Memory T Cell Response in Intestinal Tissues during Local Infection. Rhesus Macaque Killer Cell Ig-like Receptor Domain 0 Glycans Impact Surface Expression and Ligand Specificity. Suppression of Class Switch Recombination to IgA by RASA2 and RASA3 through Inhibition of TGF-β Signaling. The Marginal Zone B Cell Compartment and T Cell-independent Antibody Responses Are Supported by B Cell Intrinsic Expression of IRF1.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1