INSERM U986, Hôpital Cochin/Saint-Vincent de Paul, Paris, France.
Eur J Immunol. 2011 Dec;41(12):3574-85. doi: 10.1002/eji.201141751. Epub 2011 Nov 10.
Invariant natural killer T (iNKT) cells are a distinct lineage of innate-like T lymphocytes and converging studies in mouse models have demonstrated the protective role of iNKT cells in the development of type 1 diabetes. Recently, a new subset of iNKT cells, producing high levels of the pro-inflammatory cytokine IL-17, has been identified (iNKT17 cells). Since this cytokine has been implicated in several autoimmune diseases, we have analyzed iNKT17 cell frequency, absolute number and phenotypes in the pancreas and lymphoid organs in non-obese diabetic (NOD) mice. The role of iNKT17 cells in the development of diabetes was investigated using transfer experiments. NOD mice exhibit a higher frequency and absolute number of iNKT17 cells in the lymphoid organs as compared with C57BL/6 mice. iNKT17 cells infiltrate the pancreas of NOD mice where they express IL-17 mRNA. Contrary to the protective role of CD4(+) iNKT cells, the CD4(-) iNKT cell population, which contains iNKT17 cells, enhances the incidence of diabetes. Treatment with a blocking anti-IL-17 antibody prevents the exacerbation of the disease. This study reveals that different iNKT cell subsets play distinct roles in the regulation of type 1 diabetes and iNKT17 cells, which are abundant in NOD mice, exacerbate diabetes development.
固有自然杀伤 T(iNKT)细胞是一种独特的先天样 T 淋巴细胞谱系，在小鼠模型中的汇聚研究表明 iNKT 细胞在 1 型糖尿病的发展中具有保护作用。最近，已经鉴定出一种新型 iNKT 细胞亚群，其产生高水平的促炎细胞因子 IL-17(iNKT17 细胞)。由于这种细胞因子与几种自身免疫性疾病有关，我们分析了非肥胖型糖尿病 (NOD) 小鼠胰腺和淋巴器官中 iNKT17 细胞的频率、绝对数量和表型。通过转移实验研究了 iNKT17 细胞在糖尿病发展中的作用。与 C57BL/6 小鼠相比，NOD 小鼠的淋巴器官中 iNKT17 细胞的频率和绝对数量更高。iNKT17 细胞浸润 NOD 小鼠的胰腺，在那里它们表达 IL-17 mRNA。与 CD4(+)iNKT 细胞的保护作用相反，含有 iNKT17 细胞的 CD4(-)iNKT 细胞群增强了糖尿病的发病率。用阻断抗 IL-17 抗体治疗可防止疾病恶化。这项研究表明，不同的 iNKT 细胞亚群在 1 型糖尿病的调节中发挥不同的作用，而在 NOD 小鼠中丰富的 iNKT17 细胞会加剧糖尿病的发展。
