Department of Microbiology and Immunology, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden.
Department of Microbiology and Immunology and Department of Medicine, Albert Einstein College of Medicine, Bronx, New York, USA.
Mucosal Immunol. 2018 Jan;11(1):131-143. doi: 10.1038/mi.2017.34. Epub 2017 Apr 12.
CD1d-restricted invariant natural killer T (iNKT) cells are known as potent early regulatory cells of immune responses. Besides the established roles in the regulation of inflammation and autoimmune disease, studies have shown that iNKT cells have important roles in tumor surveillance and the control of tumor metastasis. Here we found that the absence of iNKT cells markedly decreased the total number of intestinal polyps in APC mice, a model for colorectal cancer. Polyp iNKT cells were enriched for interleukin-10 (IL-10)- and IL-17-producing cells, showed a distinct phenotype being CD4, NK1.1 CD44, and PD-1, and they were negative for the NKT cell transcription factor promyelocytic leukemia zinc-finger. The absence of iNKT cells was associated with a reduced frequency of regulatory T (Tregs) cells and lower expression levels of FoxP3 protein and transcript uniquely in the polyps, and a switch to an inflammatory macrophage phenotype. Moreover, in iNKT cell-deficient APC mice, expression of T-helper (TH) 1-associated genes, such as IFN-γ and Nos2, was increased in polyps, concomitantly with elevated frequencies of conventional CD4 and CD8 T cells in this tissue. The results suggest that a population of regulatory iNKT cells locally promote intestinal polyp formation by enhancing Treg cells and immunosuppression of antitumor TH1 immunity.
CD1d 限制性先天自然杀伤 T(iNKT)细胞被认为是免疫反应的早期调节细胞。除了在炎症和自身免疫性疾病的调节中发挥已确立的作用外，研究还表明 iNKT 细胞在肿瘤监测和控制肿瘤转移方面具有重要作用。在这里，我们发现 iNKT 细胞缺失明显减少了 APC 小鼠（结直肠癌模型）肠道息肉的总数。息肉 iNKT 细胞富含白细胞介素-10(IL-10)和白细胞介素-17 产生细胞，表现出独特的表型，即 CD4、NK1.1 CD44 和 PD-1，并且它们对 NKT 细胞转录因子早幼粒细胞白血病锌指呈阴性。iNKT 细胞缺失与调节性 T(Treg)细胞频率降低以及 FoxP3 蛋白和转录物在息肉中的表达水平降低有关，并且向炎症性巨噬细胞表型转变。此外，在 iNKT 细胞缺陷 APC 小鼠中，TH1 相关基因（如 IFN-γ 和 Nos2）的表达在息肉中增加，同时该组织中常规 CD4 和 CD8 T 细胞的频率升高。结果表明，一群调节性 iNKT 细胞通过增强 Treg 细胞和抑制抗肿瘤 TH1 免疫来局部促进肠道息肉的形成。
