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Recruitment and Maintenance of CX3CR1+CD4+ T Cells during Helminth Infection
The Journal of Immunology ( IF 4.4 ) Pub Date : 2024-01-05 , DOI: 10.4049/jimmunol.2300451
Denis G. Loredan 1, 2 , Joseph C. Devlin 1 , Kamal M. Khanna 1, 3 , P’ng Loke 4
Affiliation  

Abstract Distinct subsets of T lymphocytes express CX3CR1 under inflammatory conditions, but little is known about CX3CR1+CD4+ T cells during type 2 inflammation in helminth infections. In this study, we used a fate-mapping mouse model to characterize CX3CR1+CD4+ T cells during both acute Nippostrongylus brasiliensis and chronic Schistosoma mansoni murine models of helminth infections, revealing CX3CR1+CD4+ T cells to be an activated tissue-homing subset with varying capacity for cytokine production. Tracking these cells over time revealed that maintenance of CX3CR1 itself along with a TH2 phenotype conferred a survival advantage in the inflamed tissue. Single-cell RNA sequencing analysis of fate-mapped CX3CR1+CD4+ T cells from both the peripheral tissue and the spleen revealed a considerable level of diversity and identified a distinct population of BCL6+TCF-1+PD1+CD4+ T cells in the spleen during helminth infections. Conditional deletion of BCL6 in CX3CR1+ cells resulted in fewer CX3CR1+CD4+ T cells during infection, indicating a role in sustaining CD4+ T cell responses to helminth infections. Overall, our studies revealed the behavior and heterogeneity of CX3CR1+CD4+ T cells during type 2 inflammation in helminth infections and identified BCL6 to be important in their maintenance.

中文翻译:

蠕虫感染期间 CX3CR1+CD4+ T 细胞的招募和维持

摘要不同的 T 淋巴细胞亚群在炎症条件下表达 CX3CR1,但对于蠕虫感染的 2 型炎症期间的 CX3CR1+CD4+ T 细胞知之甚少。在这项研究中,我们使用命运图谱小鼠模型来表征急性巴西圆线虫和慢性曼氏血吸虫蠕虫感染小鼠模型中的 CX3CR1+CD4+ T 细胞,揭示 CX3CR1+CD4+ T 细胞是一种激活的组织归巢子集,具有不同的功能。细胞因子产生的能力。随着时间的推移跟踪这些细胞表明,CX3CR1 本身的维持以及 TH2 表型赋予了发炎组织的生存优势。对来自外周组织和脾脏的命运图谱 CX3CR1+CD4+ T 细胞进行单细胞 RNA 测序分析,揭示了相当大的多样性,并在蠕虫感染。CX3CR1+细胞中BCL6的条件性缺失导致感染期间CX3CR1+CD4+T细胞减少,表明其在维持CD4+T细胞对蠕虫感染的反应中发挥作用。总体而言,我们的研究揭示了蠕虫感染中 2 型炎症期间 CX3CR1+CD4+ T 细胞的行为和异质性,并确定 BCL6 在其维持中发挥重要作用。
更新日期:2024-01-05
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