The role of Interleukin-38 in modulating T cells in chronic Colitis: A mouse model study

IF 3.7 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Cytokine Pub Date : 2024-09-28 DOI:10.1016/j.cyto.2024.156769

Ying Xu , Xuan Zhang , Shanshan Liu , Nanfang Qu , Yi Gao , Changlong Lu , Jingbo Zhai , Junfeng Zhu

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引用次数: 0

Abstract

Background

Interleukin (IL)-38 belongs to the IL-36 subfamily within the IL-1 family. Patients with inflammatory bowel diseases (IBD) exhibit higher levels of IL-38 in their intestinal tissue compared to healthy controls, suggesting that IL-38 may play a role in the pathogenesis of IBD. However, IL-38′s impact on T cell-mediated immune responses in gastrointestinal inflammation has not been investigated. Therefore, the objective of this work was to elucidate the role of IL-38 in modulating T cells in a mouse model of dextran sulfate sodium (DSS)-induced chronic colitis.

Methods

Recombinant IL-38 (rIL-38) was administered intraperitoneally (i.p.) to mice with chronic colitis induced by DSS. Clinical symptoms, length of colon, and histologic alterations were assessed. Cytokine production was quantified using ELISA, and helper T (Th) cell subsets were evaluated via flow cytometry.

Results

Administration of recombinant IL-38 (rIL-38) alleviated DSS-induced chronic colitis. In addition, animals with chronic colitis treated with rIL-38 exhibited a significant decrease in the spontaneous production of inflammatory cytokines by neutrophils in the lamina propria. Furthermore, rIL-38 treatment increased the absolute numbers and percentages of regulatory T cells (Tregs) but decreased the absolute numbers and percentages of Th1 and Th17 cells. Moreover, rIL-38 treatment also decreased IL-17A-producing γδT cells substantially.

Conclusion

This study’s results show that IL-38 reduces the effects of chronic colitis caused by DSS by boosting Treg reactions and reducing Th1/Th17 reactions and IL-17A-producing γδT cells in LPL. Therefore, we propose that IL-38 has the potential to be utilized as a biological therapy agent for IBD.

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白细胞介素-38 在慢性结肠炎中调节 T 细胞的作用：小鼠模型研究

背景：白细胞介素（IL）-38 属于 IL-1 家族中的 IL-36 亚家族。与健康对照组相比，炎症性肠病（IBD）患者肠道组织中的 IL-38 水平较高，这表明 IL-38 可能在 IBD 的发病机制中发挥作用。然而，IL-38 对胃肠道炎症中 T 细胞介导的免疫反应的影响尚未得到研究。因此，本研究旨在阐明 IL-38 在右旋糖酐硫酸钠（DSS）诱导的慢性结肠炎小鼠模型中调节 T 细胞的作用：方法：对右旋糖酐硫酸钠（DSS）诱导的慢性结肠炎小鼠腹腔注射重组IL-38（rIL-38）。对小鼠的临床症状、结肠长度和组织学改变进行评估。使用 ELISA 对细胞因子的产生进行量化，并通过流式细胞术评估辅助 T（Th）细胞亚群：结果：服用重组IL-38（rIL-38）可缓解DSS诱导的慢性结肠炎。此外，接受 rIL-38 治疗的慢性结肠炎动物固有膜中性粒细胞自发产生的炎性细胞因子显著减少。此外，rIL-38 治疗增加了调节性 T 细胞（Tregs）的绝对数量和百分比，但减少了 Th1 和 Th17 细胞的绝对数量和百分比。此外，rIL-38 治疗还大幅减少了产生 IL-17A 的 γδT 细胞：结论：本研究结果表明，IL-38能增强Treg反应，减少LPL中的Th1/Th17反应和产生IL-17A的γδT细胞，从而减轻DSS引起的慢性结肠炎的影响。因此，我们认为 IL-38 有潜力用作 IBD 的生物治疗剂。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cytokine 医学-免疫学

CiteScore

7.60

自引率

2.60%

发文量

262

审稿时长

48 days

期刊介绍： The journal Cytokine has an open access mirror journal Cytokine: X, sharing the same aims and scope, editorial team, submission system and rigorous peer review. * Devoted exclusively to the study of the molecular biology, genetics, biochemistry, immunology, genome-wide association studies, pathobiology, diagnostic and clinical applications of all known interleukins, hematopoietic factors, growth factors, cytotoxins, interferons, new cytokines, and chemokines, Cytokine provides comprehensive coverage of cytokines and their mechanisms of actions, 12 times a year by publishing original high quality refereed scientific papers from prominent investigators in both the academic and industrial sectors. We will publish 3 major types of manuscripts: 1) Original manuscripts describing research results. 2) Basic and clinical reviews describing cytokine actions and regulation. 3) Short commentaries/perspectives on recently published aspects of cytokines, pathogenesis and clinical results.