Plasmacytoid Dendritic Cells Contribute to the Protective Immunity Induced by Intranasal Treatment with Fc-fused Interleukin-7 against Lethal Influenza Virus Infection.
- Author:
Moon Cheol KANG
1
;
Han Wook PARK
;
Dong Hoon CHOI
;
Young Woo CHOI
;
Yunji PARK
;
Young Chul SUNG
;
Seung Woo LEE
Author Information
- Publication Type:Brief Communication
- Keywords: Interleukin-7; Fc fusion protein; Orthomyxoviridae; Dendritic cells; T-Lymphocytes
- MeSH: Cell Movement; Dendritic Cells*; Fingolimod Hydrochloride; Humans; Influenza A virus; Influenza, Human*; Interleukin-7*; Lung; Lymph Nodes; Lymphocytes; Orthomyxoviridae*; T-Lymphocytes
- From:Immune Network 2017;17(5):343-351
- CountryRepublic of Korea
- Language:English
- Abstract: 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(RM)-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.