Exposure to ionizing radiation (IR) causes severe injuries to the human body, and normal tissue toxicity also limits the further application of cancer radiotherapy. However, current clinically used radioprotective agents are difficult to produce satisfactory effects. Toll-Like receptor (TLR) is a kind of pattern recognition receptor (PRR) that has been extensively studied for radioprotection in recent years. Several TLR family members are closely related to radioprotection. In cultured cells, TLR2, TLR5 or TLR9 agonist was proved to inhibit radiation-induced apoptosis and increase cell survival. TLR5 ligand CBLB502 was reported to alleviate bone marrow and intestinal injuries in mice and rhesus monkeys. Activation of TLR4 by its agonist LPS can protect bone marrow damage and lower mice mortality after irradiation. TLR9 ligand also exhibited protective effects on mid jejunum. Moreover, some kinds of TLR agonists, such as TLR2/6 co-agonist CBLB613, were reported to be more effective in radioprotection than single TLR agonist. In conclusion, TLRs and their ligands provide novel strategies for radiation protection in nuclear accidents as well as protection of normal tissues during cancer radiotherapy.
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