Cell-surface Milieu Remodeling in Human Dendritic Cell Activation
Dendritic cells (DCs) are specialized sentinel and APCs coordinating innate and adaptive immunity. Through proteins on their cell surface, DCs sense changes in the environment, internalize pathogens, present processed Ags, and communicate with other immune cells. By combining chemical labeling and quantitative mass spectrometry, we systematically profiled and compared the cell-surface proteomes of human primary conventional DCs (cDCs) in their resting and activated states. TLR activation by a lipopeptide globally reshaped the cell-surface proteome of cDCs, with >100 proteins upregulated or downregulated. By simultaneously elevating positive regulators and reducing inhibitory signals across multiple protein families, the remodeling creates a cell-surface milieu promoting immune responses. Still, cDCs maintain the stimulatory-to-inhibitory balance by leveraging a distinct set of inhibitory molecules. This analysis thus uncovers the molecular complexity and plasticity of the cDC cell surface and provides a roadmap for understanding cDC activation and signaling.
Authors
- Zuzhi Jiang (ORCID: https://orcid.org/0009-0009-1402-8235)
- Mark M. Davis (ORCID: https://orcid.org/0000-0001-6868-657X)
- Namrata D. Udeshi (ORCID: https://orcid.org/0000-0001-5312-1402)
- Shihong Max Gao (ORCID: https://orcid.org/0000-0003-3238-8348)
- Steven A. Carr (ORCID: https://orcid.org/0000-0002-7203-4299)
- Charles Xu (ORCID: https://orcid.org/0000-0002-7007-4035)
- Wei Luo (ORCID: https://orcid.org/0000-0003-2826-1723)
- Jun Li (ORCID: https://orcid.org/0000-0003-4353-5761)
- Qian Yin (ORCID: https://orcid.org/0009-0006-3756-1954)
Institutions
- Broad Institute (US)
- Howard Hughes Medical Institute (US)
- Janelia Research Campus (US)
- Peking University (CN)
- Institute of Infection and Immunity (CA)
- Indiana University School of Medicine
- Indiana University – Purdue University Indianapolis (US)
- The University of Texas at Austin (US)
- Stanford University (US)
Publication Details
- Journal
- The Journal of Immunology
- Published
- 2024-08-12
- DOI
- https://doi.org/10.4049/jimmunol.2400089
- Citations
- 5
- Primary Topic
- Immunotherapy and Immune Responses
- Type
- article
- Field-Weighted Citation Impact
- 1.20
Funders
- Howard Hughes Medical Institute
- Bill and Melinda Gates Foundation
- Dr. Miriam and Sheldon G. Adelson Medical Research Foundation
- Broad Institute
- Open Philanthropy Project
- Scheme for Promotion of Academic and Research Collaboration
- National Institutes of Health