Molecular Control of Plasmacytoid Dendritic Cell Development and Function

浆细胞样树突状细胞发育和功能的分子控制

• 批准号: 10583989
• 负责人: Boris Reizis
• 金额: $ 61.79万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-01 至 2028-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10583989
• 关键词: Address; Antiviral Response; Autoimmune Diseases; Autoimmunity; Award; Cell Lineage; Cellular biology; Dendritic Cells; Development; E protein; Goals; Heterogeneity; Homeostasis; Immune response; Infection; Instruction; Interferon Type I; Interferon alpha; Interferons; Methods; Molecular; Nucleic Acids; Play; Production; Regulation; Role; Specific qualifier value; TCF7L2 gene; Therapeutic; Transcriptional Regulation; Virus; Work; cell type; genetic approach; high dimensionality; human disease; in vivo; novel; response; single cell analysis; therapeutic target; translational approach

Plasmacytoid dendritic cells (pDCs) rapidly secrete type I interferon (interferon α/β, IFN) in response to virus- derived nucleic acids, facilitating both innate and adaptive antiviral responses. Conversely, aberrant IFN production by pDCs is associated with autoimmune diseases, establishing pDCs as important emerging therapeutic targets. The overall goal of this project is to elucidate the molecular control of pDCs lineage, including its development, homeostasis and function in various immune responses. In the previous award cycles, we have identified E protein transcription factor TCF4 (E2-2) and several other factors as important regulators of pDC development. The proposed work will build upon these findings to address major unanswered questions in pDC biology. In Aim 1, we will use high-dimensional single-cell analysis methods to characterize the stage and regulation of pDC lineage specification, as well as the functional heterogeneity of mature pDCs. In Aim 2, we will use genetic approaches to dissect transcriptional control and regulation of the unique IFN-producing capacity of pDCs. In Aim 3, we will explore the mechanism of virus recognition and IFN production by pDCs in vivo. Collectively, the proposed studies should yield a comprehensive molecular view of pDC development and function, paving the way for therapeutic approaches focused on this cell type. RELEVANCE (See instructions): Plasmacytoid dendritic cells (pDCs) play an important role in immune responses to infection and in autoimmunity, and therefore represent attractive targets for novel immunoterapies. The proposed work aims to build a comprehensive molecular view of pDC development and function, paving the way for pDCfocused translational approaches in human diseases.

浆细胞样树突状细胞（pDCs）响应病毒-快速分泌I型干扰素（干扰素α/β， IFN）

项目成果

The role of dendritic cells in autoimmunity.

• DOI: 10.1038/nri3477
• 发表时间: 2013-08
• 期刊: Nature reviews. Immunology

Plasmacytoid dendritic cells: recent progress and open questions.

• DOI: 10.1146/annurev-immunol-031210-101345
• 发表时间: 2011
• 期刊: Annual review of immunology
• 影响因子: 29.7
• 作者: Reizis B;Bunin A;Ghosh HS;Lewis KL;Sisirak V
• 通讯作者: Sisirak V

Kinetics of adult hematopoietic stem cell differentiation in vivo.

• DOI: 10.1084/jem.20180136
• 发表时间: 2018-11-05
• 期刊: The Journal of experimental medicine
• 作者: Upadhaya S;Sawai CM;Papalexi E;Rashidfarrokhi A;Jang G;Chattopadhyay P;Satija R;Reizis B
• 通讯作者: Reizis B

Plasmacytoid Dendritic Cells Are Largely Dispensable for the Pathogenesis of Experimental Inflammatory Bowel Disease.

• DOI: 10.3389/fimmu.2018.02475
• 发表时间: 2018
• 期刊: Frontiers in immunology
• 影响因子: 7.3
• 作者: Sawai CM;Serpas L;Neto AG;Jang G;Rashidfarrokhi A;Kolbeck R;Sanjuan MA;Reizis B;Sisirak V
• 通讯作者: Sisirak V

Continuous expression of the transcription factor e2-2 maintains the cell fate of mature plasmacytoid dendritic cells.

• DOI: 10.1016/j.immuni.2010.11.023
• 发表时间: 2010-12-14
• 期刊: Immunity
• 影响因子: 32.4
• 作者: Ghosh HS;Cisse B;Bunin A;Lewis KL;Reizis B
• 通讯作者: Reizis B