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一种新型脂质肽,具有促进平衡的效应器调节性 T 细胞反应的潜力。

A novel lipidic peptide with potential to promote balanced effector-regulatory T cell responses.

机构信息

InterK Peptide Therapeutics Limited, New South Wales, Australia.

Concept Life Sciences, Edinburgh, Scotland.

出版信息

Sci Rep. 2022 Jul 1;12(1):11185. doi: 10.1038/s41598-022-15455-5.

Abstract

T cell-dendritic cell (DC) interactions contribute to reciprocal stimulation leading to DC maturation that results in production of interleukin-12 (IL-12) and interferon-gamma (IFN-γ). Both cytokines have been implicated in autoimmune diseases while being necessary for effective immune responses against foreign antigens. We describe a lipidic peptide, designated IK14004, that modifies crosstalk between T cells and DCs resulting in suppression of IL-12p40/IFN-γ production. T cell production of interleukin-2 (IL-2) and IFN-γ is uncoupled and IL-12p70 production is enhanced. IK14004 induces expression of activating co-receptors in CD8+ T cells and increases the proportion of Foxp3-expressing CD4+ T regulatory cells. The potential for IK14004 to impact on signalling pathways required to achieve a balanced immune response upon stimulation of DCs and T cells is highlighted. This novel compound provides an opportunity to gain further insights into the complexity of T cell-DC interactions relevant to autoimmunity associated with malignancies and may have therapeutic benefit.

摘要

T 细胞-树突状细胞(DC)相互作用有助于相互刺激,导致 DC 成熟,从而产生白细胞介素-12(IL-12)和干扰素-γ(IFN-γ)。这两种细胞因子都与自身免疫性疾病有关,同时也是针对外来抗原产生有效免疫反应所必需的。我们描述了一种脂质肽,命名为 IK14004,它可以修饰 T 细胞和 DC 之间的串扰,从而抑制 IL-12p40/IFN-γ 的产生。IK14004 诱导 CD8+T 细胞表达激活共受体,并增加表达 Foxp3 的 CD4+T 调节细胞的比例。IK14004 有可能影响刺激 DC 和 T 细胞时实现平衡免疫反应所需的信号通路,这一点得到了强调。这种新型化合物为深入了解与恶性肿瘤相关的自身免疫相关的 T 细胞-DC 相互作用的复杂性提供了机会,并可能具有治疗益处。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c6d/9249808/55820defb48d/41598_2022_15455_Fig1_HTML.jpg

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