Lennard Dalit, Chin Wee Tan, Amania A. Sheikh, Ryan Munnings, Lauren J. Howson, Carolina Alvarado, Tabinda Hussain, Aidil Zaini, Lucy Cooper, Alana Kirn, Lauren Hailes, Angela Nguyen, Bailey E. Williams, Ming Z. M. Zheng, Carolien E. van de Sandt, Laura K. Mackay, Katie L. Flanagan, Katherine Kedzierska, Nicola Harris, Jennifer A. Juno, Colby Zaph, Nicole L. La Gruta, Melissa J. Davis, Stephen L. Nutt, Kim L. Good-Jacobson, Vanessa L. Bryant, Joanna R. Groom
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引用次数: 0
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. Dalit, Tan and colleagues provide a multiomic profile of T follicular helper (TFH) cells responses to diverse pathogens, revealing a blueprint for transcriptional flexibility and new tools to interrogate TFH heterogeneity in mice and humans.
期刊介绍:
Nature Immunology is a monthly journal that publishes the highest quality research in all areas of immunology. The editorial decisions are made by a team of full-time professional editors. The journal prioritizes work that provides translational and/or fundamental insight into the workings of the immune system. It covers a wide range of topics including innate immunity and inflammation, development, immune receptors, signaling and apoptosis, antigen presentation, gene regulation and recombination, cellular and systemic immunity, vaccines, immune tolerance, autoimmunity, tumor immunology, and microbial immunopathology. In addition to publishing significant original research, Nature Immunology also includes comments, News and Views, research highlights, matters arising from readers, and reviews of the literature. The journal serves as a major conduit of top-quality information for the immunology community.