Fc-fused IL-7 provides broad antiviral effects against respiratory virus infections through IL-17A-producing pulmonary innate-like T cells

Dong il Kwon; Subin Park; Yujin L. Jeong; Young Min Kim; Jeongyong Min; Changhyung Lee; Jung ah Choi; Yoon Ha Choi; Hyun Jung Kong; Youngwon Choi; Seungtae Baek; Kun Joo Lee; Yeon Woo Kang; Chaerim Jeong; Gihoon You; Youngsik Oh; Sun Kyoung Im; Manki Song; Jong Kyoung Kim; Jun Chang; Donghoon Choi; Seung Woo Lee

doi:10.1016/j.xcrm.2023.101362

Fc-fused IL-7 provides broad antiviral effects against respiratory virus infections through IL-17A-producing pulmonary innate-like T cells

Dong il Kwon, Subin Park, Yujin L. Jeong, Young Min Kim, Jeongyong Min, Changhyung Lee, Jung ah Choi, Yoon Ha Choi, Hyun Jung Kong, Youngwon Choi, Seungtae Baek, Kun Joo Lee, Yeon Woo Kang, Chaerim Jeong, Gihoon You, Youngsik Oh, Sun Kyoung Im, Manki Song, Jong Kyoung Kim, Jun ChangDonghoon Choi, Seung Woo Lee

Department of Pharmaceutical Sciences

Research output: Contribution to journal › Article › peer-review

2 Scopus citations

Abstract

Repeated pandemics caused by the influenza virus and severe acute respiratory syndrome coronavirus (SARS-CoV) have resulted in serious problems in global public health, emphasizing the need for broad-spectrum antiviral therapeutics against respiratory virus infections. Here, we show the protective effects of long-acting recombinant human interleukin-7 fused with hybrid Fc (rhIL-7-hyFc) against major respiratory viruses, including influenza virus, SARS-CoV-2, and respiratory syncytial virus. Administration of rhIL-7-hyFc in a therapeutic or prophylactic regimen induces substantial antiviral effects. During an influenza A virus (IAV) infection, rhIL-7-hyFc treatment increases pulmonary T cells composed of blood-derived interferon γ (IFNγ)+ conventional T cells and locally expanded IL-17A+ innate-like T cells. Single-cell RNA transcriptomics reveals that rhIL-7-hyFc upregulates antiviral genes in pulmonary T cells and induces clonal expansion of type 17 innate-like T cells. rhIL-7-hyFc-mediated disease prevention is dependent on IL-17A in both IAV- and SARS-CoV-2-infected mice. Collectively, we suggest that rhIL-7-hyFc can be used as a broadly active therapeutic for future respiratory virus pandemic.

Original language	English
Article number	101362
Journal	Cell Reports Medicine
Volume	5
Issue number	1
DOIs	https://doi.org/10.1016/j.xcrm.2023.101362
State	Published - 16 Jan 2024

Bibliographical note

Publisher Copyright:
© 2023 The Authors

Keywords

SARS-CoV-2
influenza A virus
innate-like T cells
interleukin-17A
interleukin-7
virus infection

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.xcrm.2023.101362

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Kwon, D. I., Park, S., Jeong, Y. L., Kim, Y. M., Min, J., Lee, C., Choi, J. A., Choi, Y. H., Kong, H. J., Choi, Y., Baek, S., Lee, K. J., Kang, Y. W., Jeong, C., You, G., Oh, Y., Im, S. K., Song, M., Kim, J. K., ... Lee, S. W. (2024). Fc-fused IL-7 provides broad antiviral effects against respiratory virus infections through IL-17A-producing pulmonary innate-like T cells. Cell Reports Medicine, 5(1), Article 101362. https://doi.org/10.1016/j.xcrm.2023.101362

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title = "Fc-fused IL-7 provides broad antiviral effects against respiratory virus infections through IL-17A-producing pulmonary innate-like T cells",

abstract = "Repeated pandemics caused by the influenza virus and severe acute respiratory syndrome coronavirus (SARS-CoV) have resulted in serious problems in global public health, emphasizing the need for broad-spectrum antiviral therapeutics against respiratory virus infections. Here, we show the protective effects of long-acting recombinant human interleukin-7 fused with hybrid Fc (rhIL-7-hyFc) against major respiratory viruses, including influenza virus, SARS-CoV-2, and respiratory syncytial virus. Administration of rhIL-7-hyFc in a therapeutic or prophylactic regimen induces substantial antiviral effects. During an influenza A virus (IAV) infection, rhIL-7-hyFc treatment increases pulmonary T cells composed of blood-derived interferon γ (IFNγ)+ conventional T cells and locally expanded IL-17A+ innate-like T cells. Single-cell RNA transcriptomics reveals that rhIL-7-hyFc upregulates antiviral genes in pulmonary T cells and induces clonal expansion of type 17 innate-like T cells. rhIL-7-hyFc-mediated disease prevention is dependent on IL-17A in both IAV- and SARS-CoV-2-infected mice. Collectively, we suggest that rhIL-7-hyFc can be used as a broadly active therapeutic for future respiratory virus pandemic.",

keywords = "SARS-CoV-2, influenza A virus, innate-like T cells, interleukin-17A, interleukin-7, virus infection",

author = "Kwon, {Dong il} and Subin Park and Jeong, {Yujin L.} and Kim, {Young Min} and Jeongyong Min and Changhyung Lee and Choi, {Jung ah} and Choi, {Yoon Ha} and Kong, {Hyun Jung} and Youngwon Choi and Seungtae Baek and Lee, {Kun Joo} and Kang, {Yeon Woo} and Chaerim Jeong and Gihoon You and Youngsik Oh and Im, {Sun Kyoung} and Manki Song and Kim, {Jong Kyoung} and Jun Chang and Donghoon Choi and Lee, {Seung Woo}",

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year = "2024",

month = jan,

day = "16",

doi = "10.1016/j.xcrm.2023.101362",

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Kwon, DI, Park, S, Jeong, YL, Kim, YM, Min, J, Lee, C, Choi, JA, Choi, YH, Kong, HJ, Choi, Y, Baek, S, Lee, KJ, Kang, YW, Jeong, C, You, G, Oh, Y, Im, SK, Song, M, Kim, JK, Chang, J, Choi, D & Lee, SW 2024, 'Fc-fused IL-7 provides broad antiviral effects against respiratory virus infections through IL-17A-producing pulmonary innate-like T cells', Cell Reports Medicine, vol. 5, no. 1, 101362. https://doi.org/10.1016/j.xcrm.2023.101362

TY - JOUR

T1 - Fc-fused IL-7 provides broad antiviral effects against respiratory virus infections through IL-17A-producing pulmonary innate-like T cells

AU - Kwon, Dong il

AU - Park, Subin

AU - Jeong, Yujin L.

AU - Kim, Young Min

AU - Min, Jeongyong

AU - Lee, Changhyung

AU - Choi, Jung ah

AU - Choi, Yoon Ha

AU - Kong, Hyun Jung

AU - Choi, Youngwon

AU - Baek, Seungtae

AU - Lee, Kun Joo

AU - Kang, Yeon Woo

AU - Jeong, Chaerim

AU - You, Gihoon

AU - Oh, Youngsik

AU - Im, Sun Kyoung

AU - Song, Manki

AU - Kim, Jong Kyoung

AU - Chang, Jun

AU - Choi, Donghoon

AU - Lee, Seung Woo

PY - 2024/1/16

Y1 - 2024/1/16

N2 - Repeated pandemics caused by the influenza virus and severe acute respiratory syndrome coronavirus (SARS-CoV) have resulted in serious problems in global public health, emphasizing the need for broad-spectrum antiviral therapeutics against respiratory virus infections. Here, we show the protective effects of long-acting recombinant human interleukin-7 fused with hybrid Fc (rhIL-7-hyFc) against major respiratory viruses, including influenza virus, SARS-CoV-2, and respiratory syncytial virus. Administration of rhIL-7-hyFc in a therapeutic or prophylactic regimen induces substantial antiviral effects. During an influenza A virus (IAV) infection, rhIL-7-hyFc treatment increases pulmonary T cells composed of blood-derived interferon γ (IFNγ)+ conventional T cells and locally expanded IL-17A+ innate-like T cells. Single-cell RNA transcriptomics reveals that rhIL-7-hyFc upregulates antiviral genes in pulmonary T cells and induces clonal expansion of type 17 innate-like T cells. rhIL-7-hyFc-mediated disease prevention is dependent on IL-17A in both IAV- and SARS-CoV-2-infected mice. Collectively, we suggest that rhIL-7-hyFc can be used as a broadly active therapeutic for future respiratory virus pandemic.

AB - Repeated pandemics caused by the influenza virus and severe acute respiratory syndrome coronavirus (SARS-CoV) have resulted in serious problems in global public health, emphasizing the need for broad-spectrum antiviral therapeutics against respiratory virus infections. Here, we show the protective effects of long-acting recombinant human interleukin-7 fused with hybrid Fc (rhIL-7-hyFc) against major respiratory viruses, including influenza virus, SARS-CoV-2, and respiratory syncytial virus. Administration of rhIL-7-hyFc in a therapeutic or prophylactic regimen induces substantial antiviral effects. During an influenza A virus (IAV) infection, rhIL-7-hyFc treatment increases pulmonary T cells composed of blood-derived interferon γ (IFNγ)+ conventional T cells and locally expanded IL-17A+ innate-like T cells. Single-cell RNA transcriptomics reveals that rhIL-7-hyFc upregulates antiviral genes in pulmonary T cells and induces clonal expansion of type 17 innate-like T cells. rhIL-7-hyFc-mediated disease prevention is dependent on IL-17A in both IAV- and SARS-CoV-2-infected mice. Collectively, we suggest that rhIL-7-hyFc can be used as a broadly active therapeutic for future respiratory virus pandemic.

KW - SARS-CoV-2

KW - influenza A virus

KW - innate-like T cells

KW - interleukin-17A

KW - interleukin-7

KW - virus infection

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DO - 10.1016/j.xcrm.2023.101362

M3 - Article

C2 - 38232693

AN - SCOPUS:85182580227

SN - 2666-3791

VL - 5

JO - Cell Reports Medicine

JF - Cell Reports Medicine

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M1 - 101362

ER -

Fc-fused IL-7 provides broad antiviral effects against respiratory virus infections through IL-17A-producing pulmonary innate-like T cells

Abstract

Bibliographical note

Keywords

UN SDGs

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