澳大利亚沃尔特和伊丽莎·霍尔医学研究所Joanna R. Groom小组取得一项新突破。他们的最新研究揭示了不同的细胞因子和转录特征控制功能性T滤泡辅助细胞异质性。这一研究成果于2025年9月9日发表在国际顶尖学术期刊《自然—免疫学》上。

为了揭示T_FH表型的多样性是如何建立的，该研究组分析了非主题T_FH细胞对病毒、蠕虫和细菌感染的反应。课题组确定了一个与CD4⁺ T滤泡调节细胞和效应细胞不同的核心T_FH特征，并确定了塑造T_FH功能的病原体特异性转录模块。细胞因子转录T_FH编程表明，I型干扰素和TGFβ信号直接指示个体T_FH表型，指导B细胞输出。细胞因子导向的T_FH转录表型在人类生发中心内是共享的，但不同的T_FH表型在供体之间和免疫挑战后或抗体介导的疾病中占主导地位。最后，该团队确定了与不同T_FH表型一致的新的细胞表面标记。因此，研究组提供了人类和小鼠中T_FH多样性的全面抵抗，以便在感染和疾病期间进行免疫监测，并为开发特定情况的疫苗提供信息。

据介绍，CD4⁺ T滤泡辅助细胞（T_FH）支持针对多种病原体的量身定制的B细胞反应。

附：英文原文

Title: Divergent cytokine and transcriptional signatures control functional T follicular helper cell heterogeneity

Author: Dalit, Lennard, Tan, Chin Wee, Sheikh, Amania A., Munnings, Ryan, Howson, Lauren J., Alvarado, Carolina, Hussain, Tabinda, Zaini, Aidil, Cooper, Lucy, Kirn, Alana, Hailes, Lauren, Nguyen, Angela, Williams, Bailey E., Zheng, Ming Z. M., van de Sandt, Carolien E., Mackay, Laura K., Flanagan, Katie L., Kedzierska, Katherine, Harris, Nicola, Juno, Jennifer A., Zaph, Colby, La Gruta, Nicole L., Davis, Melissa J., Nutt, Stephen L., Good-Jacobson, Kim L., Bryant, Vanessa L., Groom, Joanna R.

Issue&Volume: 2025-09-09

Abstract: CD4+ T follicular helper (TFH) cells support tailored B cell responses against multiple classes of pathogens. To reveal how diverse TFH phenotypes are established, we profiled mouse TFH cells in response to viral, helminth and bacterial infection. We identified a core TFH signature that is distinct from CD4+ T follicular regulatory and effector cells and identified pathogen-specific transcriptional modules that shape TFH function. Cytokine-transcriptional TFH programming demonstrated that type I interferon and TGFβ signaling direct individual TFH phenotypes to instruct B cell output. Cytokine-directed TFH transcriptional phenotypes are shared within human germinal centers, but distinct TFH phenotypes dominate between donors and following immune challenge or in antibody-mediated disease. Finally, we identified new cell surface markers that align with distinct TFH phenotypes. Thus, we provide a comprehensive resource of TFH diversity in humans and mice to enable immune monitoring during infection and disease and to inform the development of context-specific vaccines.

DOI: 10.1038/s41590-025-02258-9

Source: https://www.nature.com/articles/s41590-025-02258-9