Harnessing lipid signaling pathways to target specialized pro-angiogenic neutrophil subsets for regenerative immunotherapy
| Autor: | Gabriel A. Kwong, Hong Seo Lim, F. S. Pittman, Thomas C. Turner, Edward A. Botchwey, Quoc D. Mac, William Y. York, Peng Qiu, Mary Caitlin P. Sok, L. A. Hymel, S. Vyshnya |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Docosahexaenoic Acids
Neutrophils medicine.medical_treatment Immunology Context (language use) Biology CXCR4 03 medical and health sciences 0302 clinical medicine Engineering medicine Macrophage Humans Research Articles 030304 developmental biology Inflammation 0303 health sciences Multidisciplinary integumentary system SciAdv r-articles Dendritic cell Lipid signaling Immunotherapy biochemical phenomena metabolism and nutrition Cell biology 030220 oncology & carcinogenesis Wound healing Reprogramming Research Article Signal Transduction |
| Zdroj: | Science Advances |
| ISSN: | 2375-2548 |
| Popis: | Local delivery of a pro-resolving lipid mediator leads to a shift in the immune microenvironment and improves wound healing. To gain insights into neutrophil heterogeneity dynamics in the context of sterile inflammation and wound healing, we performed a pseudotime analysis of single-cell flow cytometry data using the spanning-tree progression analysis of density-normalized events algorithm. This enables us to view neutrophil transitional subsets along a pseudotime trajectory and identify distinct VEGFR1, VEGFR2, and CXCR4 high-expressing pro-angiogenic neutrophils. While the proresolving lipid mediator aspirin-triggered resolvin D1 (AT-RvD1) has a known ability to limit neutrophil infiltration, our analysis uncovers a mode of action in which AT-RvD1 leads to inflammation resolution through the selective reprogramming toward a therapeutic neutrophil subset. This accumulation leads to enhanced vascular remodeling in the skinfold window chamber and a proregenerative shift in macrophage and dendritic cell phenotype, resulting in improved wound closure after skin transplantation. As the targeting of functional immune subsets becomes the key to regenerative immunotherapies, single-cell pseudotime analysis tools will be vital in this field. |
| Databáze: | OpenAIRE |
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