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

Autor:	Kwon DI; Department of Life Sciences, Pohang University of Science and Technology, Pohang 37666, Republic of Korea., Park S; Department of Life Sciences, Pohang University of Science and Technology, Pohang 37666, Republic of Korea., Jeong YL; Department of Life Sciences, Pohang University of Science and Technology, Pohang 37666, Republic of Korea., Kim YM; Department of Life Sciences, Pohang University of Science and Technology, Pohang 37666, Republic of Korea., Min J; Department of Life Sciences, Pohang University of Science and Technology, Pohang 37666, Republic of Korea., Lee C; Department of Life Sciences, Pohang University of Science and Technology, Pohang 37666, Republic of Korea., Choi JA; Science Unit, International Vaccine Institute, Seoul 08826, Republic of Korea., Choi YH; Department of Life Sciences, Pohang University of Science and Technology, Pohang 37666, Republic of Korea., Kong HJ; Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul 03760, Republic of Korea., Choi Y; Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul 03760, Republic of Korea., Baek S; Research Institute of NeoImmuneTech Co., Ltd., Pohang 37666, Republic of Korea., Lee KJ; Department of Life Sciences, Pohang University of Science and Technology, Pohang 37666, Republic of Korea., Kang YW; Department of Life Sciences, Pohang University of Science and Technology, Pohang 37666, Republic of Korea., Jeong C; Department of Life Sciences, Pohang University of Science and Technology, Pohang 37666, Republic of Korea., You G; Department of Life Sciences, Pohang University of Science and Technology, Pohang 37666, Republic of Korea., Oh Y; Department of Life Sciences, Pohang University of Science and Technology, Pohang 37666, Republic of Korea., Im SK; Research Institute of NeoImmuneTech Co., Ltd., Pohang 37666, Republic of Korea., Song M; Science Unit, International Vaccine Institute, Seoul 08826, Republic of Korea., Kim JK; Department of Life Sciences, Pohang University of Science and Technology, Pohang 37666, Republic of Korea., Chang J; Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul 03760, Republic of Korea., Choi D; Research Institute of NeoImmuneTech Co., Ltd., Pohang 37666, Republic of Korea. Electronic address: dhchoi@neoimmunetech.com., Lee SW; Department of Life Sciences, Pohang University of Science and Technology, Pohang 37666, Republic of Korea. Electronic address: sw_lee@postech.ac.kr.
Jazyk:	angličtina
Zdroj:	Cell reports. Medicine [Cell Rep Med] 2024 Jan 16; Vol. 5 (1), pp. 101362.
DOI:	10.1016/j.xcrm.2023.101362
Abstrakt:	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. Competing Interests: Declaration of interests The authors declare no competing interests. (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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