Radiation-induced interferon-I response impairs thyroid organoid function

Background and AimRadiotherapy is a standard cancer treatment, but radiation exposure to surrounding healthy tissues may lead to adverse side effects that compromise patient quality of life. In patients with head and neck cancer treated with radiotherapy, thyroid damage is a frequent complication, resulting in hypothyroidism or secondary thyroid malignancies. Although clinically recognized, the molecular mechanisms underlying these side effects remain mostly unexplored. This study aims to characterize the radiation-induced molecular alterations in thyroid organoids. MethodsBulk RNA sequencing was performed to investigate transcriptomic changes in tissue-derived thyroid organoids following gamma-irradiation. Observed changes were further validated and explored using qPCRs, western blotting, immunofluorescence, caspase 3/7 activity and organoid forming efficiency. ResultsOur findings identify interferon-{beta} (IFN-{beta}) signaling as a key mediator of radiation-induced inflammation in the thyroid. Additionally, the intrinsic apoptotic pathway was found to be the predominant mechanism of radiation-induced thyroid cell death. Notably, while IFN-{beta} exhibited a protective effect against apoptosis, it concurrently reduced thyroid stem progenitor cell potential. ConclusionsThese results highlight the dual role of IFN-{beta} signaling in modulating thyroid cell fate after irradiation, potentially promoting survival upon injury at the expense of regenerative potential.