Mechanism Of Innate Lymphoid Cells Regulate Radiation-induced Skin Damage Via CCR10 Signaling

Objective:Skin damage caused by radiation therapy（radiodermatitis）is a severe side effect of radiotherapy in cancer patients.Innate lymphoid cells（ILCs）,which are abundant in the skin,played important roles in innate immunity.ILCs isolated from the skin of healthy people express CCR10.In the previous study,we use CCR10^+/-and CCR10^-/-mice to assess the role of CCR10 in ILCs response in radiation-induced chronic dermatitis and acute dermatitis.Methods:The mice with CCR10^+/-and CCR10^-/-genotype were irradiated by a single dose of 5 Gy or 5 Gy/day for 6 days with a total dose of 30 Gy with high-energy X-ray.The ILCs from the skin of irradiated and control mice were sorted and analyzed by flow cytometry 3 days and 10 days after irradiation.Also,a mouse model of radiodermatitis was used to assess the skin damage 10 days after fractionated irradiation.Results:The number of ILCs were decreased in both CCR10^+/-and CCR10^-/-mice 3days after single irradiation.However,the skin inflammation recovered and ILCs restored to normal levels on 10 days after single irradiation.Although the ILCs of both genotypes are decreasing after fractionated irradiation,the ratio of ILCs in CCR10^+/-mice skin was higher than that in CCR10^-/-mice skin on 10 days after irradiation.The results from Immunohistochemistry revealed that the skin inflammation of CCR10^-/-mice was severer than that of CCR10^+/-mice.There were no significant differences in ILCs between different genotypes mice in spleen and blood.Conclusion:Our results showed that CCR10^+/-mice had a higher ratio of ILCs and less skin damage than CCR10^-/-mice after irradiation.These findings indicated that the ILCs were regulated by CCR10 which might be a potential therapeutic target for reducing the severity of radiodermatitis.