Type 1 conventional dendritic cell fate and function are controlled by DC-SCRIPT
Journal Title
Science Immunology
Abstract
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.
Publisher
AAAS
WEHI Research Division(s)
Immunology; Advanced Technology And Biology; Bioinformatics; Blood Cells And Blood Cancer; Infectious Diseases And Immune Defence
PubMed ID
33811060
NHMRC Grants
NHMRC/1054925
Rights Notice
Refer to copyright notice on published article.


Creation Date: 2021-04-28 08:16:00
Last Modified: 2021-05-06 09:57:37
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