Type I IFN promotes ILC2-to-ILC1 plasticity in pre-clinical radiation-induced lung injury
Abstract
Radiation-induced lung injury (RILI) is a common dose-limiting toxicity after radiotherapy for lung cancer, but the immunological mechanisms contributing to RILI pathogenesis remain poorly understood. Here we analyze a RILI mouse model using high-dose, restricted-field irradiation to the left lung. Flow cytometry and cytokine profiling analysis of innate lymphoid cells (ILC) reveals a radiation-induced shift from lung-resident type 2 ILCs (ILC2) toward pro-inflammatory type 1 ILCs (ILC1). Single-cell RNA-sequencing analysis of mouse lung ILC populations after radiation suggests that type I interferon (IFN) promotes radiation-induced ILC2-to-ILC1 plasticity. In vitro, IFN-β stimulation of mouse ILC2s leads to increased expression of the ILC1 markers T-bet and IFN-γ, while IFN-β stimulation of human peripheral blood mononuclear cells increases the ILC1-to-ILC2 ratio. In vivo, inhibition of type I IFN signaling attenuates lung damage after irradiation in our RILI model. Thus, our findings indicate that radiation-induced type I IFN induces ILC2-to-ILC1 plasticity to contribute to RILI pathogenesis, and suggest that targeting type I IFN signaling may be a therapeutic strategy to mitigate radiation-induced lung injury.
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BibTeX
@article{kim2026type,
title = {{Type I IFN promotes ILC2-to-ILC1 plasticity in pre-clinical radiation-induced lung injury}},
author = {Jaeho Kim and Haiqing Li and Rifat Mannan and Taylor A. Doherty and Heather M. McGee},
journal = {Nature Communications},
year = {2026},
month = oct,
doi = {10.1038/s41467-026-77637-3},
url = {https://www.nature.com/articles/s41467-026-77637-3},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Type I IFN promotes ILC2-to-ILC1 plasticity in pre-clinical radiation-induced lung injury
AU - Jaeho Kim
AU - Haiqing Li
AU - Rifat Mannan
AU - Taylor A. Doherty
AU - Heather M. McGee
PY - 2026
DA - 2026/10/20
JO - Nature Communications
DO - 10.1038/s41467-026-77637-3
UR - https://www.nature.com/articles/s41467-026-77637-3
AB - Radiation-induced lung injury (RILI) is a common dose-limiting toxicity after radiotherapy for lung cancer, but the immunological mechanisms contributing to RILI pathogenesis remain poorly understood. Here we analyze a RILI mouse model using high-dose, restricted-field irradiation to the left lung. Flow cytometry and cytokine profiling analysis of innate lymphoid cells (ILC) reveals a radiation-induced shift from lung-resident type 2 ILCs (ILC2) toward pro-inflammatory type 1 ILCs (ILC1). Single-cell RNA-sequencing analysis of mouse lung ILC populations after radiation suggests that type I interferon (IFN) promotes radiation-induced ILC2-to-ILC1 plasticity. In vitro, IFN-β stimulation of mouse ILC2s leads to increased expression of the ILC1 markers T-bet and IFN-γ, while IFN-β stimulation of human peripheral blood mononuclear cells increases the ILC1-to-ILC2 ratio. In vivo, inhibition of type I IFN signaling attenuates lung damage after irradiation in our RILI model. Thus, our findings indicate that radiation-induced type I IFN induces ILC2-to-ILC1 plasticity to contribute to RILI pathogenesis, and suggest that targeting type I IFN signaling may be a therapeutic strategy to mitigate radiation-induced lung injury.
SN - 2041-1723
ER -