Interleukin-14 Prevents Cytarabine or Irradiation Induced Neutropenia via JAK/STAT3 Signaling.

IF 1.1 4区医学 Q4 IMMUNOLOGY

Iranian Journal of Immunology Pub Date : 2025-06-23 DOI:10.22034/iji.2025.105019.2925

Shengnan Xu, Chaoqiong Ye, Zhihua Wu, Chuying Wen, Wenhui Huang, Cong Deng, Jiaye Hua, Wei Xie, Min Xiao

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引用次数: 0

Abstract

Background: Severe neutropenia significantly increases the risk of bacterial infections. Recent studies have shown that the cytokine interleukin 14 (IL-14) plays an important role in immune cells, but its potential role in neutropenia induced by cytarabine (ara-c) or irradiation is unclear.

Objective: To investigate the role of IL-14 in ara-c or irradiation-induced neutropenia.

Methods: Two neutropenia models were induced by ara-c or irradiation. Neutrophil count was confirmed through flow cytometry and routine blood tests. IL-14 was used to assess the impact on neutropenia. IL-14 expression was analyzed using qPCR, Western blotting and ELISA. A IL-14 receptor (IL-14R) knockout mice model was utilized to confirm the role of IL-14R/STAT3 signaling in vivo.

Results: The results indicated that IL-14 treatment promoted proliferation and increased neutrophil counts in both bone marrow and peripheral blood, while IL-14R knockout suppressed this process. Furthermore, the downstream molecule of IL-14R, STAT3, showed enhanced phosphorylation levels in the presence of IL-14. Finally, we explored the source of IL-14 in the bone marrow, and found that lymphocytes secreted the highest levels of IL-14. Serum levels of IL-14 were significantly reduced in patients after chemotherapy.

Conclusions: These results indicate that IL-14 prevents ara-c or irradiation-induced neutropenia by regulating lymphocytes and activating the IL-14R/STAT3 pathway in neutrophils. This evidence suggests that IL-14 is a potent cytokine for treating ara-c or irradiation-induced neutropenia.

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白细胞介素-14通过JAK/STAT3信号阻止阿糖胞苷或辐照诱导的中性粒细胞减少。

背景：严重中性粒细胞减少显著增加细菌感染的风险。最近的研究表明，细胞因子白细胞介素14 （IL-14）在免疫细胞中起重要作用，但其在阿糖胞苷（ara-c）或辐照诱导的中性粒细胞减少症中的潜在作用尚不清楚。目的：探讨白细胞介素-14 （IL-14）在ara-c或辐照致中性粒细胞减少症中的作用。方法：采用ara-c和辐照诱导两种中性粒细胞减少模型。通过流式细胞术和血常规检查确认中性粒细胞计数。IL-14用于评估对中性粒细胞减少症的影响。采用qPCR、Western blotting和ELISA检测IL-14的表达。利用IL-14受体（IL-14R）敲除小鼠模型来证实IL-14R/STAT3信号在体内的作用。结果：结果表明，IL-14处理促进了骨髓和外周血的增殖，增加了中性粒细胞计数，而IL-14R敲除抑制了这一过程。此外，IL-14R的下游分子STAT3在IL-14存在下表现出磷酸化水平的增强。最后，我们探索了骨髓中IL-14的来源，发现淋巴细胞分泌的IL-14水平最高。化疗后患者血清IL-14水平明显降低。结论：这些结果表明，IL-14通过调节淋巴细胞和激活中性粒细胞中的IL-14R/STAT3通路来预防ara-c或辐照诱导的中性粒细胞减少症。这一证据表明，IL-14是治疗ara-c或辐照诱导的中性粒细胞减少症的有效细胞因子。

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

Iranian Journal of Immunology Medicine-Immunology and Allergy

CiteScore

1.60

自引率

0.00%

发文量

审稿时长

12 weeks

期刊介绍： The Iranian Journal of Immunology (I.J.I) is an internationally disseminated peer-reviewed publication and publishes a broad range of experimental and theoretical studies concerned with all aspects of immunology.