Harnessing invariant natural killer T cells to control pathological inflammation.
Harnessing invariant natural killer T cells to control pathological inflammation.
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DOI：
10.3389/fimmu.2022.998378
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发表时间：
2022
影响因子：
7.3
通讯作者：
Gumperz, Jenny E. E.
中科院分区：
文献类型：
--
作者：
Bharadwaj, Nikhila S. S.;Gumperz, Jenny E. E.
不变自然杀伤 T (iNKT) 细胞是先天性 T 细胞，因其强大的免疫调节功能而受到认可。在过去的三十年里，对小鼠模型的研究和人类观察研究表明，iNKT 细胞可以在多种情况下限制炎症病理。由于 iNKT 细胞具有多功能性，并且在某些情况下可以促进炎症，因此了解其抗炎作用的机制基础对于有效利用它们进行临床应用至关重要。已经出现了两种截然不同的机制来解释 iNKT 细胞的抗炎活性：它们驱动其他调节细胞介导的抑制途径，并且它们可以通过细胞溶解消除促进过度炎症反应的抗原呈递细胞。如何控制这些活动并将其与其促炎功能分开仍然是一个中心问题。小鼠 iNKT 细胞可分为四个功能谱系，具有促炎（NKT1、NKT17）或抗炎（NKT2、NKT10）细胞因子谱。然而，在人类中，这些亚群并不明显，相反，大多数 CD4+ iNKT 细胞似乎倾向于产生多功能 (TH0) 细胞因子，而 CD4- iNKT 细胞似乎更倾向于细胞溶解活性。此外，在小鼠模型中，结构不同的抗原已被证明可诱导 iNKT 细胞产生 TH1 或 TH2 偏向反应，但人类 iNKT 细胞可能以无法完全区分 TH1 和 TH2 细胞因子产生的方式对不同水平的 TCR 刺激作出反应。我们讨论了这些差异对于专注于 iNKT 细胞抗炎活性的转化工作的影响。
Invariant natural killer T (iNKT) cells are innate T cells that are recognized for their potent immune modulatory functions. Over the last three decades, research in murine models and human observational studies have revealed that iNKT cells can act to limit inflammatory pathology in a variety of settings. Since iNKT cells are multi-functional and can promote inflammation in some contexts, understanding the mechanistic basis for their anti-inflammatory effects is critical for effectively harnessing them for clinical use. Two contrasting mechanisms have emerged to explain the anti-inflammatory activity of iNKT cells: that they drive suppressive pathways mediated by other regulatory cells, and that they may cytolytically eliminate antigen presenting cells that promote excessive inflammatory responses. How these activities are controlled and separated from their pro-inflammatory functions remains a central question. Murine iNKT cells can be divided into four functional lineages that have either pro-inflammatory (NKT1, NKT17) or anti-inflammatory (NKT2, NKT10) cytokine profiles. However, in humans these subsets are not clearly evident, and instead most iNKT cells that are CD4+ appear oriented towards polyfunctional (TH0) cytokine production, while CD4- iNKT cells appear more predisposed towards cytolytic activity. Additionally, structurally distinct antigens have been shown to induce TH1- or TH2-biased responses by iNKT cells in murine models, but human iNKT cells may respond to differing levels of TCR stimulation in a way that does not neatly separate TH1 and TH2 cytokine production. We discuss the implications of these differences for translational efforts focused on the anti-inflammatory activity of iNKT cells.
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影响因子：
3.7
作者：
Eidson M;Wahlstrom J;Beaulieu AM;Zaidi B;Carsons SE;Crow PK;Yuan J;Wolchok JD;Horsthemke B;Wieczorek D;Sant'Angelo DB
通讯作者：
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影响因子：
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作者：
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通讯作者：
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影响因子：
5.5
作者：
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通讯作者：
Gumperz, Jenny E.
影响因子：
4.4
作者：
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通讯作者：
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影响因子：
3.2
作者：
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通讯作者：
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