The emerging role of IL-17A across different types of radiation-induced normal tissue injuries

Radiation-induced normal tissue injuries (RITIs) are the main complications that can significantly limit the use of radiotherapy and affect clinical outcomes in patients with cancer. This article aims to review current literature on the role of proinflammatory cytokine interleukin (IL)-17A in different types of RITIs. While irradiation significantly increases IL-17A expression in normal tissues, activated IL-17A plays a dual role of both promoting and protecting against RITIs, depending on the tissue type. These novel findings have led to a strong interest in evaluating the therapeutic potential of targeting IL-17A/IL-17 receptor signals in RITIs in different normal tissues. Preliminary results from preclinical animal models have shown that blocking IL-17A/IL-17 receptor signaling after irradiation significantly reduces the pathogenesis of RITIs in the skin and lung but enhances it in the intestine and oral mucosa. However, the mechanisms underlying the tissue-dependent dual roles of IL-17A in RITIs remain elusive. Therefore, future studies focusing on the precise role and mechanism of IL-17A action in different RITIs are needed.