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 Brown, Wang Cao, Nicolas Jacquelot, Angela D'Amico, Andrew M Lew, Yifan Zhan, Christopher J Tonkin, Jose A Villadangos, Gordon K Smyth, Michael Chopin, Stephen L Nutt
SCIENCE IMMUNOLOGY | AMER ASSOC ADVANCEMENT SCIENCE | Published : 2021
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..View full abstract
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Awarded by National Health and Medical Research Council of Australia
This work was supported by the National Health and Medical Research Council of Australia [1155342 and 1054925 (S.L.N.); 1143976, 1150425, and 1080321 (A.M.L.); 1058892 (G.K.S.); and 1154502, 1113293, and 1163090 (J.A.V.)] and the Melbourne research scholarship (S.Z.). M.C. is supported by the Jenny Thatchell/Pauline Speedy and the Barbara McDonald Innovation grants, H.D.C. by the Marian and E.H. Flack Fellowship, and H.D.C. and G.K.S. by the Chan Zuckerberg Initiative EOSS program. This work was made possible through the Victorian State Government Operational Infrastructure Support and Australian Government NHMRC IRIIS. The generation of the Zfp366-/-and Zfp366-tdTomato mice used in this study was supported by the Australian Phenomics Network (APN) and the Australian Government through the National Collaborative Research Infrastructure Strategy (NCRIS) program.