转化科学与治疗部和免疫治疗综合研究中心Jarrod A. Dudakov研究组报道，损伤诱导的IL-18刺激胸腺NK细胞限制内源性组织再生。该研究于2025年9月11日发表于国际一流学术期刊《自然—免疫学》杂志上。

研究团队发现成熟的IL-18在胸腺中产生，在许多不同形式的组织损伤之后，所有这些组织损伤都是caspase-1介导的免疫原性细胞死亡。该研究团队报道IL-18刺激的细胞毒性NK细胞限制内源性胸腺再生，这是确保急性损伤（如应激、感染、化疗和放疗）后免疫能力恢复的关键过程。NK细胞通过异常靶向胸腺上皮细胞抑制胸腺恢复，胸腺上皮细胞是器官功能和再生的主要调节因子。总之，他们的数据揭示了调节胸腺组织再生的新途径，并表明IL-18是促进胸腺功能的潜在治疗靶点。

此外，鉴于IL-18作为癌症免疫疗法的热情，由于其能够引发1型免疫反应，这些发现也为潜在的脱靶效应提供了见解。

据悉，白细胞介素-18 （IL-18）是一种急性期促炎分子，通过激活T辅助1 CD4⁺ T细胞、细胞毒性CD8⁺ T细胞和自然杀伤（NK）细胞介导病毒清除。

附：英文原文

Title: Damage-induced IL-18 stimulates thymic NK cells limiting endogenous tissue regeneration

Author: Granadier, David, Cooper, Kirsten, Acenas, Dante, Kousa, Anastasia, Warren, Makya, Hernandez, Vanessa, Iovino, Lorenzo, deRoos, Paul, Lederer, Emma E., Shannon-Sevillano, Steve, Kinsella, Sinad, Evandy, Cindy, van den Brink, Marcel R. M., Lemarquis, Andri, Dudakov, Jarrod A.

Issue&Volume: 2025-09-11

Abstract: Interleukin-18 (IL-18) is an acute-phase proinflammatory molecule crucial for mediating viral clearance by activating T helper 1 CD4+ T cells, cytotoxic CD8+ T cells and natural killer (NK) cells. Here, we show that mature IL-18 is generated in the thymus following numerous distinct forms of tissue damage, all of which cause caspase-1-mediated immunogenic cell death. We report that IL-18-stimulated cytotoxic NK cells limit endogenous thymic regeneration, a critical process that ensures the restoration of immune competence after acute insults such as stress, infection, chemotherapy and radiation. NK cells suppress thymus recovery by aberrantly targeting thymic epithelial cells, which act as the master regulators of organ function and regeneration. Together, our data reveal a new pathway regulating tissue regeneration in the thymus and suggest IL-18 as a potential therapeutic target to boost thymic function. Moreover, given the enthusiasm for IL-18 as a cancer immunotherapy due to its capacity to elicit a type 1 immune response, these findings also offer insight into potential off-target effects.

DOI: 10.1038/s41590-025-02270-z

Source: https://www.nature.com/articles/s41590-025-02270-z