Regulatory B-Cells Are Associated Negatively With Regulatory T-Cells and Positively With Cytokines in Peripheral Blood of Pregnant Women.

IF 2.5 3区 医学 Q3 IMMUNOLOGY
Kyle S Wiley, Laura E Martínez, Daylon Kwon, Delaney A Knorr, Marta Epeldegui, Molly M Fox
{"title":"Regulatory B-Cells Are Associated Negatively With Regulatory T-Cells and Positively With Cytokines in Peripheral Blood of Pregnant Women.","authors":"Kyle S Wiley, Laura E Martínez, Daylon Kwon, Delaney A Knorr, Marta Epeldegui, Molly M Fox","doi":"10.1111/aji.70027","DOIUrl":null,"url":null,"abstract":"<p><strong>Problem: </strong>Regulatory B-cells (Bregs, CD19<sup>+</sup>CD24<sup>hi</sup>CD38<sup>hi</sup>) are a specialized B-cell subset that suppresses immune responses and potentially contribute to the maintenance of an immune-privileged environment for fetal development during pregnancy. However, little is known about the surrounding immunological environment of Bregs in gestational physiology. The relationship of regulatory T-cells (Tregs, CD4<sup>+</sup>CD25<sup>hi</sup>CD127<sup>lo</sup>FoxP3<sup>+</sup>) to Bregs in coordinating immunoregulation during pregnancy is unknown. We aimed to determine whether peripheral concentrations of Bregs and/or PD-L1-expressing Bregs correlated with Tregs and cytokines during pregnancy.</p><p><strong>Method: </strong>Peripheral blood samples were obtained from 29 pregnant women at mean 12 weeks' gestation. Participants were age ≥ 18, self-identified as Latina/Hispanic, and N = 12 primigravid. Peripheral blood mononuclear cells were isolated, stained, and analyzed by flow cytometry to determine percentages of Tregs from CD4<sup>+</sup> T-cells and five Treg subsets defined by immune checkpoint markers, and Bregs and PD-L1<sup>+</sup> Bregs from total B-cells. Levels of 13 cytokines were measured on a Meso Scale Discovery multiplex platform.</p><p><strong>Results: </strong>Bregs positively correlated with pro-inflammatory cytokine interleukin (IL)-6. PD-L1<sup>+</sup> Bregs positively correlated with T-cell suppressive cytokine IL-10. PD-L1<sup>+</sup> Bregs negatively correlated with Tregs and Helios<sup>+</sup>, CTLA-4<sup>+</sup>, PD-1<sup>+</sup>, TIGIT<sup>+</sup>, and TIM3<sup>+</sup> Tregs. For primigravida, PD-L1<sup>+</sup> Bregs correlated positively with IL-10 and negatively with Helios<sup>+</sup> and TIGIT<sup>+</sup> Tregs. For multigravida, PD-L1<sup>+</sup> Bregs correlated positively with IL-8 and negatively with Helios<sup>+</sup>, CTLA-4<sup>+</sup>, PD-1<sup>+</sup>, and TIGIT<sup>+</sup> Tregs.</p><p><strong>Conclusions: </strong>This study provides insight into the immunosuppressive role of Bregs and PD-L1<sup>+</sup> Bregs during human pregnancy. Our results suggest that PD-L1<sup>+</sup> Bregs can employ suppressive mechanisms to limit pro-inflammatory responses in primigravida.</p>","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"93 2","pages":"e70027"},"PeriodicalIF":2.5000,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"American Journal of Reproductive Immunology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1111/aji.70027","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
引用次数: 0

Abstract

Problem: Regulatory B-cells (Bregs, CD19+CD24hiCD38hi) are a specialized B-cell subset that suppresses immune responses and potentially contribute to the maintenance of an immune-privileged environment for fetal development during pregnancy. However, little is known about the surrounding immunological environment of Bregs in gestational physiology. The relationship of regulatory T-cells (Tregs, CD4+CD25hiCD127loFoxP3+) to Bregs in coordinating immunoregulation during pregnancy is unknown. We aimed to determine whether peripheral concentrations of Bregs and/or PD-L1-expressing Bregs correlated with Tregs and cytokines during pregnancy.

Method: Peripheral blood samples were obtained from 29 pregnant women at mean 12 weeks' gestation. Participants were age ≥ 18, self-identified as Latina/Hispanic, and N = 12 primigravid. Peripheral blood mononuclear cells were isolated, stained, and analyzed by flow cytometry to determine percentages of Tregs from CD4+ T-cells and five Treg subsets defined by immune checkpoint markers, and Bregs and PD-L1+ Bregs from total B-cells. Levels of 13 cytokines were measured on a Meso Scale Discovery multiplex platform.

Results: Bregs positively correlated with pro-inflammatory cytokine interleukin (IL)-6. PD-L1+ Bregs positively correlated with T-cell suppressive cytokine IL-10. PD-L1+ Bregs negatively correlated with Tregs and Helios+, CTLA-4+, PD-1+, TIGIT+, and TIM3+ Tregs. For primigravida, PD-L1+ Bregs correlated positively with IL-10 and negatively with Helios+ and TIGIT+ Tregs. For multigravida, PD-L1+ Bregs correlated positively with IL-8 and negatively with Helios+, CTLA-4+, PD-1+, and TIGIT+ Tregs.

Conclusions: This study provides insight into the immunosuppressive role of Bregs and PD-L1+ Bregs during human pregnancy. Our results suggest that PD-L1+ Bregs can employ suppressive mechanisms to limit pro-inflammatory responses in primigravida.

求助全文
约1分钟内获得全文 求助全文
来源期刊
CiteScore
6.20
自引率
5.60%
发文量
314
审稿时长
2 months
期刊介绍: The American Journal of Reproductive Immunology is an international journal devoted to the presentation of current information in all areas relating to Reproductive Immunology. The journal is directed toward both the basic scientist and the clinician, covering the whole process of reproduction as affected by immunological processes. The journal covers a variety of subspecialty topics, including fertility immunology, pregnancy immunology, immunogenetics, mucosal immunology, immunocontraception, endometriosis, abortion, tumor immunology of the reproductive tract, autoantibodies, infectious disease of the reproductive tract, and technical news.
×
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
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
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 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信