| First Author | Zhang S | Year | 2021 |
| Journal | Sci Immunol | Volume | 6 |
| Issue | 58 | PubMed ID | 33811060 |
| Mgi Jnum | J:345531 | Mgi Id | MGI:7595960 |
| Doi | 10.1126/sciimmunol.abf4432 | Citation | Zhang S, et al. (2021) Type 1 conventional dendritic cell fate and function are controlled by DC-SCRIPT. Sci Immunol 6(58):eabf4432 |
| abstractText | The functional diversification of dendritic cells (DCs) is a key step in establishing protective immune responses. Despite the importance of DC lineage diversity, its genetic basis is not fully understood. The transcription factor DC-SCRIPT is expressed in conventional DCs (cDCs) and their committed bone marrow progenitors but not in plasmacytoid DCs (pDCs). We show that mice lacking DC-SCRIPT displayed substantially impaired development of IRF8 (interferon regulatory factor 8)-dependent cDC1, whereas cDC2 numbers increased marginally. The residual DC-SCRIPT-deficient cDC1s had impaired capacity to capture and present cell-associated antigens and to secrete IL-12p40, two functional hallmarks of this population. Genome-wide mapping of DC-SCRIPT binding and gene expression analyses revealed a key role for DC-SCRIPT in maintaining cDC1 identity via the direct regulation of cDC1 signature genes, including Irf8 Our study reveals DC-SCRIPT to be a critical component of the gene regulatory program shaping the functional attributes of cDC1s. |
