A circulating subset of iNKT cells mediates antitumor and antiviral immunity
A circulating subset of iNKT cells mediates antitumor and antiviral immunity
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DOI：
10.1126/sciimmunol.abj8760
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发表时间：
2022-10-01
影响因子：
24.8
通讯作者：
Ikuta, Koichi
中科院分区：
文献类型：
--
作者：
Cui, Guangwei;Shimba, Akihiro;Ikuta, Koichi
不变的自然杀伤T（iNKT）细胞是一组识别脂质抗原的先天性T淋巴细胞。它们被认为是组织驻留物，对于全身和局部免疫调节很重要。为了研究iNKT细胞的异质性，我们重新表征了胸腺和外周组织中的iNKT细胞。根据自然杀伤细胞受体CD 244和趋化因子受体CXCR 6的表达，将胸腺中的iNKT细胞分为三个亚群，并命名为C 0（CD 244（-）CXCR 6（-））、C1（CD 244（-）CXCR 6（+））或C2（CD 244（+）CXCR 6（+））iNKT细胞。从C 0 iNKT细胞向C2 iNKT细胞的发育和成熟严格依赖于胸腺上皮细胞产生的IL-15。C2 iNKT细胞表达高水平的IFN-γ。和颗粒酶，并表现出更多的NK细胞样特征，而C1 iNKT细胞表现出更多的T细胞样特征。C2 iNKT细胞受到微生物组和衰老的影响，并抑制了胸腺中自身免疫调节因子AIRE的表达。在外周组织中，循环的C2 iNKT细胞不同于常规的组织驻留的C1 iNKT细胞。在功能上，C2 iNKT细胞通过增强抗肿瘤免疫保护小鼠免受黑素瘤细胞的肿瘤转移，并促进针对流感病毒感染的抗病毒免疫应答。此外，我们鉴定了具有高细胞毒性特性的人CD 244（+）CXCR 6（+）iNKT细胞作为小鼠C2 iNKT细胞的对应物。因此，该研究揭示了具有NK细胞样性质的iNKT细胞的循环亚群，其不同于常规的组织驻留iNKT细胞。
Invariant natural killer T (iNKT) cells are a group of innate-like T lymphocytes that recognize lipid antigens. They are supposed to be tissue resident and important for systemic and local immune regulation. To investigate the heterogeneity of iNKT cells, we recharacterized iNKT cells in the thymus and peripheral tissues. iNKT cells in the thymus were divided into three subpopulations by the expression of the natural killer cell receptor CD244 and the chemokine receptor CXCR6 and designated as C0 (CD244(-)CXCR6(-)), C1 (CD244(-)CXCR6(+)), or C2 (CD244(+)CXCR6(+)) iNKT cells. The development and maturation of C2 iNKT cells from C0 iNKT cells strictly depended on IL-15 produced by thymic epithelial cells. C2 iNKT cells expressed high levels of IFN-. and granzymes and exhibited more NK cell-like features, whereas C1 iNKT cells showed more T cell-like characteristics. C2 iNKT cells were influenced by the microbiome and aging and suppressed the expression of the autoimmune regulator AIRE in the thymus. In peripheral tissues, C2 iNKT cells were circulating that were distinct from conventional tissue-resident C1 iNKT cells. Functionally, C2 iNKT cells protected mice from the tumor metastasis of melanoma cells by enhancing antitumor immunity and promoted antiviral immune responses against influenza virus infection. Furthermore, we identified human CD244(+)CXCR6(+) iNKT cells with high cytotoxic properties as a counterpart of mouse C2 iNKT cells. Thus, this study reveals a circulating subset of iNKT cells with NK cell-like properties distinct from conventional tissue-resident iNKT cells.