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10.3389/fimmu.2021.697840

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suck abstract from ncbi


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pmid34394090      Front+Immunol 2021 ; 12 (ä): 697840
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  • CD169 Defines Activated CD14(+) Monocytes With Enhanced CD8(+) T Cell Activation Capacity #MMPMID34394090
  • Affandi AJ; Olesek K; Grabowska J; Nijen Twilhaar MK; Rodriguez E; Saris A; Zwart ES; Nossent EJ; Kalay H; de Kok M; Kazemier G; Stockl J; van den Eertwegh AJM; de Gruijl TD; Garcia-Vallejo JJ; Storm G; van Kooyk Y; den Haan JMM
  • Front Immunol 2021[]; 12 (ä): 697840 PMID34394090show ga
  • Monocytes are antigen-presenting cells (APCs) that play diverse roles in promoting or regulating inflammatory responses, but their role in T cell stimulation is not well defined. In inflammatory conditions, monocytes frequently show increased expression of CD169/Siglec-1, a type-I interferon (IFN-I)-regulated protein. However, little is known about the phenotype and function of these CD169(+) monocytes. Here, we have investigated the phenotype of human CD169(+) monocytes in different diseases, their capacity to activate CD8(+) T cells, and the potential for a targeted-vaccination approach. Using spectral flow cytometry, we detected CD169 expression by CD14(+) CD16(-) classical and CD14(+) CD16(+) intermediate monocytes and unbiased analysis showed that they were distinct from dendritic cells, including the recently described CD14-expressing DC3. CD169(+) monocytes expressed higher levels of co-stimulatory and HLA molecules, suggesting an increased activation state. IFNalpha treatment highly upregulated CD169 expression on CD14(+) monocytes and boosted their capacity to cross-present antigen to CD8(+) T cells. Furthermore, we observed CD169(+) monocytes in virally-infected patients, including in the blood and bronchoalveolar lavage fluid of COVID-19 patients, as well as in the blood of patients with different types of cancers. Finally, we evaluated two CD169-targeting nanovaccine platforms, antibody-based and liposome-based, and we showed that CD169(+) monocytes efficiently presented tumor-associated peptides gp100 and WT1 to antigen-specific CD8(+) T cells. In conclusion, our data indicate that CD169(+) monocytes are activated monocytes with enhanced CD8(+) T cell stimulatory capacity and that they emerge as an interesting target in nanovaccine strategies, because of their presence in health and different diseases.
  • |Antigen Presentation/*immunology[MESH]
  • |CD8-Positive T-Lymphocytes/*immunology[MESH]
  • |COVID-19/immunology[MESH]
  • |Carcinoma, Pancreatic Ductal/immunology[MESH]
  • |Cells, Cultured[MESH]
  • |Flow Cytometry[MESH]
  • |Humans[MESH]
  • |Influenza, Human/immunology[MESH]
  • |Interferon-alpha/pharmacology[MESH]
  • |Lipopolysaccharide Receptors/metabolism[MESH]
  • |Lung Neoplasms/immunology[MESH]
  • |Lymphocyte Activation/*immunology[MESH]
  • |Monocytes/*immunology[MESH]
  • |Pancreatic Neoplasms/immunology[MESH]
  • |SARS-CoV-2/immunology[MESH]


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