月经周期通过CCR5信号调节女性生殖道中CD4 T细胞迁移监测。

IF 7.9 2区 医学 Q1 IMMUNOLOGY Mucosal Immunology Pub Date : 2024-02-01 DOI:10.1016/j.mucimm.2023.10.002
M. Elliott Williams , Felica P. Hardnett , Anandi N. Sheth , Alexander N. Wein , Zheng-Rong Tiger Li , Jessica Radzio-Basu , Chuong Dinh , Lisa B. Haddad , Elizabeth M.B. Collins , Igho Ofotokun , Rustom Antia , Christopher D. Scharer , J. Gerardo Garcia-Lerma , Jacob E. Kohlmeier , Alison Swaims-Kohlmeier
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引用次数: 0

摘要

尽管它们对性传播感染(STIs)的免疫力很重要,但女性生殖道(FRT)记忆T细胞群的组成在月经周期调节下对局部组织环境变化的反应仍不明确。在这里,我们发现,在人类和猪尾猕猴中,该周期通过与迁移记忆(TMM)和驻留记忆(TRM)细胞相对应的亚群来决定不同的CD4 T细胞监测行为。TMM表现出组织巡回运输特征,在FRT微环境中的分布受限,以及对感染的不同效应反应。通过RNA测序的基因通路分析确定了TMM特异性富集的参与激素调节和炎症反应的基因。发现FRT细胞亚群波动与周期驱动的CCR5信号同步。值得注意的是,口服CCR5拮抗剂药物阻断了TMM的贩运。总之,这项研究为FRT记忆CD4 T细胞的动态性质提供了新的见解,并确定月经周期是STI病原体暴露部位免疫监测的关键调节因子。
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The menstrual cycle regulates migratory CD4 T-cell surveillance in the female reproductive tract via CCR5 signaling

Despite their importance for immunity against sexually transmitted infections, the composition of female reproductive tract (FRT) memory T-cell populations in response to changes within the local tissue environment under the regulation of the menstrual cycle remains poorly defined. Here, we show that in humans and pig-tailed macaques, the cycle determines distinct clusters of differentiation 4 T-cell surveillance behaviors by subsets corresponding to migratory memory (TMM) and resident memory T cells. TMM displays tissue-itinerant trafficking characteristics, restricted distribution within the FRT microenvironment, and distinct effector responses to infection. Gene pathway analysis by RNA sequencing identified TMM-specific enrichment of genes involved in hormonal regulation and inflammatory responses. FRT T-cell subset fluctuations were discovered that synchronized to cycle-driven CCR5 signaling. Notably, oral administration of a CCR5 antagonist drug blocked TMM trafficking. Taken together, this study provides novel insights into the dynamic nature of FRT memory CD4 T cells and identifies the menstrual cycle as a key regulator of immune surveillance at the site of STI pathogen exposure.

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来源期刊
Mucosal Immunology
Mucosal Immunology 医学-免疫学
CiteScore
16.60
自引率
3.80%
发文量
100
审稿时长
12 days
期刊介绍: Mucosal Immunology, the official publication of the Society of Mucosal Immunology (SMI), serves as a forum for both basic and clinical scientists to discuss immunity and inflammation involving mucosal tissues. It covers gastrointestinal, pulmonary, nasopharyngeal, oral, ocular, and genitourinary immunology through original research articles, scholarly reviews, commentaries, editorials, and letters. The journal gives equal consideration to basic, translational, and clinical studies and also serves as a primary communication channel for the SMI governing board and its members, featuring society news, meeting announcements, policy discussions, and job/training opportunities advertisements.
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