不寻常的嫌疑犯——先天淋巴细胞作为 IBD 的新治疗靶点。

The unusual suspects--innate lymphoid cells as novel therapeutic targets in IBD.

机构信息

Department of Experimental Immunobiology, Division of Transplantation Immunology and Mucosal Biology, London SE1 9RT, UK.

Department of Medical and Molecular Genetics, King's College London, London SE1 9RT, UK.

出版信息

Nat Rev Gastroenterol Hepatol. 2015 May;12(5):271-83. doi: 10.1038/nrgastro.2015.52.

Abstract

Innate lymphoid cells (ILCs) are a family of immune cells that selectively accumulate in mucosal tissues serving as sentinels at the vanguard of host protective immunity. However, they are also implicated as cellular mediators of immune-mediated diseases, most notably IBD. ILCs are subdivided into distinct lineages based on the expression of effector cytokines and master transcription factors that programme their differentiation and inflammatory behaviour. Strikingly, these subsets closely resemble CD4(+) T-cell lineages, including T helper (TH)1, TH2 and TH17 cells that are similarly implicated in immune-mediated diseases. However, ILCs that promote the maintenance of intestinal epithelial cells, mostly through production of IL-22, also exist. ILCs rapidly respond to environmental cues, including cytokines, metabolic signals and luminal bacteria. They are potent and immediate producers of key cytokines linked to IBD pathogenesis, including TNF, IL-17, IL-22 and IFN-γ. Some subsets are implicated as mediators of chronic intestinal inflammation, whereas others might provide protective functions. They are present in the gut of patients with IBD and, intriguingly, closer scrutiny of IBD susceptibility loci shows that many of these genes are either expressed by, or are intimately linked to, ILC function. Looking forward, targeting ILCs could represent a new IBD treatment paradigm.

摘要

先天淋巴细胞(ILCs)是一类免疫细胞,它们选择性地在黏膜组织中积聚,作为宿主保护性免疫的前沿哨兵。然而,它们也被认为是免疫介导性疾病的细胞介导物,尤其是炎症性肠病(IBD)。ILCs 根据效应细胞因子和主转录因子的表达进行细分,这些因子编程它们的分化和炎症行为。引人注目的是,这些亚群与 CD4(+) T 细胞亚群非常相似,包括辅助性 T(TH)1、TH2 和 TH17 细胞,这些细胞也同样与免疫介导性疾病有关。然而,也存在促进肠上皮细胞维持的 ILCs,主要通过产生 IL-22。ILCs 可以迅速响应环境线索,包括细胞因子、代谢信号和腔细菌。它们是与 IBD 发病机制相关的关键细胞因子的有效和即时产生者,包括 TNF、IL-17、IL-22 和 IFN-γ。一些亚群被认为是慢性肠道炎症的介导物,而其他亚群可能提供保护功能。它们存在于 IBD 患者的肠道中,有趣的是,对 IBD 易感性基因座的更仔细研究表明,这些基因中的许多要么由 ILC 表达,要么与 ILC 功能密切相关。展望未来,靶向 ILCs 可能代表一种新的 IBD 治疗范式。

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