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Plasmacytoid Dendritic Cells Contribute to the Protective Immunity Induced by Intranasal Treatment with Fc-fused Interleukin-7 against Lethal Influenz

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Editor, Senior Moderator
Immune Netw. 2017 Oct;17(5):343-351. doi: 10.4110/in.2017.17.5.343. Epub 2017 Oct 24.
[h=1]Plasmacytoid Dendritic Cells Contribute to the Protective Immunity Induced by Intranasal Treatment with Fc-fused Interleukin-7 against Lethal Influenza Virus Infection.[/h] Kang MC[SUP]1[/SUP], Park HW[SUP]1[/SUP], Choi DH[SUP]2[/SUP], Choi YW[SUP]1[/SUP], Park Y[SUP]1[/SUP], Sung YC[SUP]1,[/SUP][SUP]2,[/SUP][SUP]3[/SUP], Lee SW[SUP]1,[/SUP][SUP]3[/SUP].
[h=3]Author information[/h]

[h=3]Abstract[/h] Developing a novel vaccine that can be applied against multiple strains of influenza virus is of utmost importance to human health. Previously, we demonstrated that the intranasal introduction of Fc-fused IL-7 (IL-7-mFc), a long-acting cytokine fusion protein, confers long-lasting prophylaxis against multiple strains of influenza A virus (IAV) by inducing the development of lung-resident memory-like T cells, called T[SUB]RM[/SUB]-like cells. Here, we further investigated the mechanisms of IL-7-mFc-mediated protective immunity to IAVs. First, we found that IL-7-mFc treatment augments the accumulation of pulmonary T cells in 2 ways: recruiting blood circulating T cells into the lung and expanding T cells at the lung parenchyma. Second, the blockade of T cell migration from the lymph nodes (LNs) with FTY720 treatment was not required for mounting the protective immunity to IAV with IL-7-mFc, suggesting a more important role of IL-7 in T cells in the lungs. Third, IL-7-mFc treatment also recruited various innate immune cells into the lungs. Among these cells, plasmacytoid dendritic cells (pDCs) play an important role in IL-7-mFc-mediated protective immunity through reducing the immunopathology and increasing IAV-specific cytotoxic T lymphocyte (CTL) responses. In summary, our results show that intranasal treatment with IL-7-mFc modulates pulmonary immune responses to IAV, affecting both innate and adaptive immune cells.


[h=4]KEYWORDS:[/h] Dendritic cells; Fc fusion protein; Interleukin-7; Orthomyxoviridae; T-Lymphocytes

PMID: 29093655 PMCID: PMC5662783 DOI: 10.4110/in.2017.17.5.343
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