依托泊苷诱导蛋白2.4调控iNKT细胞的发育和IFN-γ应答（英文）

Etoposide-induced Protein 2.4 Regulates The Development and IFN-γ Production of iNKT Cells

iNKT细胞是一类特殊的固有样T淋巴细胞,在感染、肿瘤、自身性免疫疾病和代谢类疾病中都发挥重要的调控作用.揭示调控iNKT细胞发育、分化和功能的细胞分子机制,对于阐释iNKT细胞与疾病的关系以及寻求可能的治疗途径都具有重要的意义.依托泊苷诱导蛋白2.4 (Etoposide-induced protein 2.4,Ei24)可调控细胞生长、凋亡和自噬等多种生物学功能,但其对iNKT细胞的发育和功能的影响仍不清楚.本研究利用Cre/loxP重组酶系统成功构建T细胞中Ei24特异性敲除小鼠.敲除Ei24后,iNKT细胞在胸腺中的发育受到明显抑制,肝脏和脾脏等组织中的iNKT比例和数目明显减少.进一步研究发现,Ei24主要影响iNKT1和iNKT17 2个亚群,对iNKT2的调控作用相对较小.当腹腔注射iNKT细胞特异性活化抗原α-GC后,敲除Ei24后iNKT细胞的IFN-γ应答更低,但不影响i NKT细胞的IL-4应答.以上结果表明,Ei24可以调控iNKT细胞的发育与功能.

Invariant natural killer T(iNKT)cells are a subset of innate-like T cells,which play important regulatory roles in multiple diseases including infection,tumor and metabolic diseases.Revealing the cellular and molecular mechanisms that regulate the development,differentiation and function of iNKT cells is of great significance to elucidate the relationship between iNKT cells and diseases and to seek possible therapeutic approaches.Etoposide-induced protein 2.4(Ei24)is an autophagy-associated protein which involved in the regulation of cell growth and apoptosis.However,whether Ei24 could regulate iNKT cell differentiation and functions remains unclear.Here,using Cre/loxP system to specifically delete Ei24 in T cells,we found that Ei24 was required for terminal maturation of iNKT cells in thymus,liver and spleen.iNKT1 and iNKT17,but not iNKT2 cells,were affected by Ei24 deficiency.Furthermore,we found that the production of IFN-γ,but not IL-4,was impaired in Ei24 deficient iNKT cells when lipid antigenα-GC was injected in vivo.These results demonstrate that Ei24 is required for the development and function of iNKT cells.