| First Author | Huang B | Year | 2022 |
| Journal | Nat Commun | Volume | 13 |
| Issue | 1 | Pages | 805 |
| PubMed ID | 35145086 | Mgi Jnum | J:330302 |
| Mgi Id | MGI:6887001 | Doi | 10.1038/s41467-022-28378-6 |
| Citation | Huang B, et al. (2022) In vivo CRISPR screens reveal a HIF-1alpha-mTOR-network regulates T follicular helper versus Th1 cells. Nat Commun 13(1):805 |
| abstractText | T follicular helper (Tfh) cells provide signals to initiate and maintain the germinal center (GC) reaction and are crucial for the generation of robust, long-lived antibody responses, but how the GC microenvironment affects Tfh cells is not well understood. Here we develop an in vivo T cell-intrinsic CRISPR-knockout screen to evaluate Tfh and Th1 cells in an acute viral infection model to identify regulators of Tfh cells in their physiological setting. Using a screen of druggable-targets, alongside genetic, transcriptomic and cellular analyses, we identify a function of HIF-1alpha in suppressing mTORC1-mediated and Myc-related pathways, and provide evidence that VHL-mediated degradation of HIF-1alpha is required for Tfh development; an expanded in vivo CRISPR screen reveals multiple components of these pathways that regulate Tfh versus Th1 cells, including signaling molecules, cell-cycle regulators, nutrient transporters, metabolic enzymes and autophagy mediators. Collectively, our data serve as a resource for studying Tfh versus Th1 decisions, and implicate the VHL-HIF-1alpha axis in fine-tuning Tfh generation. |
