Airway fibroblasts drive IL-4-mediated Th2 polarization in airway allergy: Mechanisms and therapeutic targeting

IF 4.2 2区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimica et biophysica acta. Molecular basis of disease Pub Date : 2025-06-11 DOI:10.1016/j.bbadis.2025.167951

Lihua Mo , Le Liu , Jinbiao Xie , Jinna Yang , Gaohui Wu , Qinmiao Huang , Pingchang Yang , Xiangqian Luo

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引用次数: 0

Abstract

•
Airway fibroblasts in allergic asthma (AA) mice demonstrated a 2.3-fold increase in IL-4+ cell proportion (p < 0.01), indicating their dominant role in driving Th2 inflammation compared to CD4+ T cells (24.7 % contribution, p < 0.001).
•
Fibroblasts upregulated activation markers CD80/CD83/CD86 (p < 0.0001), which correlated with enhanced IL-4-dependent Th2 polarization (30.01 % Teffs vs. 8.89 % with naive fibroblasts, p < 0.0001), suggesting their capacity to amplify allergic responses.
•
Targeted FbNP therapy reduced pathological fibroblast frequency by 24.6 % and systemic IL-4 levels by 48.83 %, accompanied by significant suppression of Th2 cytokines (IL-5: 46.88 %; IL-13: 50.84 %, all p < 0.001), demonstrating dual anti-inflammatory and immunoregulatory effects.
•
Clinically, FbNP alleviated asthma symptoms (52–65 % reduction in airway resistance) and improved airway hyperresponsiveness (AHR, 41 % correction, p < 0.01), with sustained therapeutic efficacy for 14 days and no detectable toxicity.

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气道成纤维细胞驱动il -4介导的Th2极化：机制和治疗靶向。

•过敏性哮喘（AA）小鼠的气道成纤维细胞显示IL-4+细胞比例增加2.3倍(p <；0.01)，表明与CD4+ T细胞相比，它们在驱动Th2炎症中起主导作用(贡献24.7%,p <；0.001)。•成纤维细胞上调活化标记CD80/CD83/CD86 (p <；0.0001)，与il -4依赖性Th2极化增强相关(Teffs为30.01%，幼稚成纤维细胞为8.89%,p <；0.0001)，表明它们有放大过敏反应的能力。•靶向FbNP治疗使病理性成纤维细胞频率降低24.6%，全身IL-4水平降低48.83%，并伴有Th2细胞因子的显著抑制(IL-5: 46.88%；IL-13: 50.84%，全部p <；0.001)，显示出双重抗炎和免疫调节作用。•临床上，FbNP缓解了哮喘症状（气道阻力降低52 - 65%）并改善了气道高反应性(AHR，纠正41%，p <；0.01)，持续治疗14天，无毒副作用。

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来源期刊

Biochimica et biophysica acta. Molecular basis of disease 生物-生化与分子生物学

CiteScore

12.30

自引率

0.00%

发文量

218

审稿时长

32 days

期刊介绍： BBA Molecular Basis of Disease addresses the biochemistry and molecular genetics of disease processes and models of human disease. This journal covers aspects of aging, cancer, metabolic-, neurological-, and immunological-based disease. Manuscripts focused on using animal models to elucidate biochemical and mechanistic insight in each of these conditions, are particularly encouraged. Manuscripts should emphasize the underlying mechanisms of disease pathways and provide novel contributions to the understanding and/or treatment of these disorders. Highly descriptive and method development submissions may be declined without full review. The submission of uninvited reviews to BBA - Molecular Basis of Disease is strongly discouraged, and any such uninvited review should be accompanied by a coverletter outlining the compelling reasons why the review should be considered.