Spatiotemporal resolution of germinal center Tfh cell differentiation and divergence from central memory CD4 + T cell fate.

Autor: Zhu F; Department of Microbiology, School of Medicine, University of Alabama at Birmingham, Birmingham, AL, 35294, USA., McMonigle RJ; Department of Microbiology, School of Medicine, University of Alabama at Birmingham, Birmingham, AL, 35294, USA., Schroeder AR; Department of Microbiology, School of Medicine, University of Alabama at Birmingham, Birmingham, AL, 35294, USA., Xia X; Department of Microbiology, School of Medicine, University of Alabama at Birmingham, Birmingham, AL, 35294, USA., Figge D; Department of Pathology, School of Medicine, University of Alabama at Birmingham, Birmingham, AL, 35294, USA., Greer BD; Department of Medicine, School of Medicine, University of Alabama at Birmingham, Birmingham, AL, 35294, USA., González-Avalos E; Division of Signaling and Gene Expression, La Jolla Institute for Immunology, La Jolla, CA, 92037, USA., Sialer DO; Department of Microbiology, School of Medicine, University of Alabama at Birmingham, Birmingham, AL, 35294, USA., Wang YH; Department of Microbiology, School of Medicine, University of Alabama at Birmingham, Birmingham, AL, 35294, USA., Chandler KM; Department of Microbiology, School of Medicine, University of Alabama at Birmingham, Birmingham, AL, 35294, USA., Getzler AJ; Department of Immunology and Microbiology, The Scripps Research Institute, Jupiter, FL, 33458, USA., Brown ER; Department of Microbiology, School of Medicine, University of Alabama at Birmingham, Birmingham, AL, 35294, USA., Xiao C; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, 92037, USA., Kutsch O; Department of Medicine, School of Medicine, University of Alabama at Birmingham, Birmingham, AL, 35294, USA., Harada Y; Faculty of Pharmaceutical Sciences, Tokyo, University of Science, Chiba, 278-8510, Japan., Pipkin ME; Department of Immunology and Microbiology, The Scripps Research Institute, Jupiter, FL, 33458, USA., Hu H; Department of Microbiology, School of Medicine, University of Alabama at Birmingham, Birmingham, AL, 35294, USA. huihu@uab.edu.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2023 Jun 17; Vol. 14 (1), pp. 3611. Date of Electronic Publication: 2023 Jun 17.
DOI: 10.1038/s41467-023-39299-3
Abstrakt: Follicular helper T (Tfh) cells are essential for germinal center (GC) B cell responses. However, it is not clear which PD-1 + CXCR5 + Bcl6 + CD4 + T cells will differentiate into PD-1 hi CXCR5 hi Bcl6 hi GC-Tfh cells and how GC-Tfh cell differentiation is regulated. Here, we report that the sustained Tigit expression in PD-1 + CXCR5 + CD4 + T cells marks the precursor Tfh (pre-Tfh) to GC-Tfh transition, whereas Tigit - PD-1 + CXCR5 + CD4 + T cells upregulate IL-7Rα to become CXCR5 + CD4 + T memory cells with or without CCR7. We demonstrate that pre-Tfh cells undergo substantial further differentiation at the transcriptome and chromatin accessibility levels to become GC-Tfh cells. The transcription factor c-Maf appears critical in governing the pre-Tfh to GC-Tfh transition, and we identify Plekho1 as a stage-specific downstream factor regulating the GC-Tfh competitive fitness. In summary, our work identifies an important marker and regulatory mechanism of PD-1 + CXCR5 + CD4 + T cells during their developmental choice between memory T cell fate and GC-Tfh cell differentiation.
(© 2023. The Author(s).)
Databáze: MEDLINE
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