Type 1 conventional dendritic cell fate and function are controlled by DC-SCRIPT

Shengbo Zhang, Hannah D. Coughlan, Mitra Ashayeripanah, Simona Seizova, Andrew J. Kueh, Daniel V. Brown, Wang Cao, Nicolas Jacquelot, Angela D'Amico, Andrew M. Lew, Yifan Zhan, Christopher J. Tonkin, Jose A. Villadangos, Gordon K. Smyth, Michaël Chopin, Stephen L. Nutt

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15 Citations (Scopus)

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.

Original languageEnglish
Article numbereabf4432
Number of pages17
JournalScience Immunology
Volume6
Issue number58
DOIs
Publication statusPublished - Apr 2021
Externally publishedYes

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