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

Zhang, S; Coughlan, HD; Ashayeripanah, M; Seizova, S; Kueh, AJ; Brown, DV; Cao, W; Jacquelot, N; D&#39;Amico, A; Lew, AM; Zhan, Y; Tonkin, CJ; Villadangos, JA; Smyth, GK; Chopin, M; Nutt, SL

Author(s): Zhang, S; Coughlan, HD; Ashayeripanah, M; Seizova, S; Kueh, AJ; Brown, DV; Cao, W; Jacquelot, N; D'Amico, A; Lew, AM; Zhan, Y; Tonkin, CJ; Villadangos, JA; Smyth, GK; Chopin, M; Nutt, SL;
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
Research Division(s): Immunology; Advanced Technology And Biology; Bioinformatics; Blood Cells And Blood Cancer; Infectious Diseases And Immune Defence
PubMed ID: 33811060
Publisher's Version: https://doi.org/10.1126/sciimmunol.abf4432
NHMRC Grants: NHMRC/1054925,
Terms of Use/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