Type 1 conventional dendritic cell fate and function are controlled by DC-SCRIPT
| Autor: | Simona Seizova, Yifan Zhan, Mitra Ashayeri-Panah, Michael Chopin, Nicolas Jacquelot, Shengbo Zhang, Daniel Brown, Andrew M. Lew, Angela D'Amico, Wang Cao, Stephen L. Nutt, Gordon K. Smyth, Jose A Villadangos, Christopher J. Tonkin, Andrew J. Kueh, Hannah D. Coughlan |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Male Immunology Population Biology 03 medical and health sciences Mice 0302 clinical medicine Immune system Cross-Priming Gene expression Animals Humans Progenitor cell education Gene Transcription factor Cells Cultured Bone Marrow Transplantation Mice Knockout education.field_of_study Transplantation Chimera Nuclear Proteins Cell Differentiation General Medicine Dendritic Cells Fibroblasts Interleukin-12 Cell biology DNA-Binding Proteins Disease Models Animal 030104 developmental biology Gene Expression Regulation Interferon Regulatory Factors Female IRF8 Toxoplasma Conventional Dendritic Cell Toxoplasmosis 030215 immunology Transcription Factors |
| Zdroj: | Science immunology. 6(58) |
| ISSN: | 2470-9468 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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