[The role of IL-22 in T cell reconstitution after thymus damage induced by ionizing radiation]

Abstract

Objective: To explore the levels of IL-22 in thymus damaged by γ-ray total body irradiation (TBI), and to study the role of IL-22 in T cell reconstitution after thymic injury induced by TBI. Methods: To induce thymic injury, mice were treated by sub-lethal TBI. Levels of intra-thymic and circulatory IL-22 were detected by using ELISA assay. Untreated mice were used as control. After receiving sub-lethal TBI, mice were intraperitoneally injected with PBS or recombinant mouse IL-22, which were marked as TBI+PBS or TBI+IL-22, respectively. Mice were monitored for counts of total thymic cells and circulatory white blood cells. Flow cytometry was applied to analyze percentages of thymic epithelial cells (TEC), thymocyte subsets and circulatory T cells. Real-time PCR assay was applied to analyze the mRNA expression levels of Foxn1, Ccl25, Aire and Dll4 in thymus. Results: ①Sub-lethal TBI treated mice expressed higher levels of intra-thymic and circulatory IL-22, compared with untreated ones (all P<0.05). ②After injection of recombinant IL-22, TBI+IL-22 mice had higher levels of intra-thymic IL-22 than TBI+PBS mice (all P<0.05). ③On day 14 after irradiation, real-time PCR assay showed that TBI+IL-22 mice had higher mRNA levels of Foxn1, Ccl25, Aire and Dll4 in thymus compared with TBI+PBS ones. Meanwhile, the TBI+IL-22 mice had higher counts of total thymic cells[(5.93±3.19)×10(6)/ml vs (1.42±0.46)×10(6)/ml, t=3.128, P=0.033] and circulatory white blood cells[(3.08±0.94)×10(6)/ml vs (1.43±0.30)×10(6)/ml, t=3.730, P=0.015] than those of TBI+PBS mice. Flow cytometry analysis indicated that TBI+IL-22 mice had higher counts of TEC and thymocytes than TBI+PBS mice on day 14 after irradiation (all P<0.05). On days 7 and 14 after irradiation, TBI+IL-22 mice had higher counts of circulatory white blood cells and T cells than TBI+PBS mice (all P<0.05). Conclusion: Sub-lethal TBI induces upregulation of intra-thymic IL-22, and injecting of recombinant IL-22 increases level of IL-22 in thymus. Injecting of recombinant IL-22 improves recovery of TEC and increases numbers of thymocyte subsets and circulatory T cell after thymic injury.

Keywords: IL-22; T cell reconstitution; Thymus; Total body irradiation.

图1. 全身照射（TBI）前后小鼠胸腺内（A）及血浆（B）中IL-22表达水平变化（设3个复孔，*P<0.05）