Fibrosis is defined as excessive deposition of the extracellular matrix (ECM) in the parenchyma of various organs, and sometimes leads to irreversible organ malfunction such as idiopathic pulmonary fibrosis (IPF), a fatal disorder of the lung. Chronic inflammatory stimuli induce fibrotic responses in various organs. Various immune cells, including T helper (Th) cells in the lung, protect the host from different harmful particles, including pathogenic microorganisms. However, the dysregulation of the function of these immune cells in the lung sometimes causes inflammatory diseases, such as lung fibrosis. In this review, we will introduce an outline of the cellular and molecular mechanisms underlying the pathogenic fibrotic responses in the lung. We will also introduce the concept of the “Pathogenic Th population disease induction model,” in which unique subpopulations of certain Th cell subsets control the pathology of immune-mediated inflammatory diseases. Finally, we introduce our recent findings, which demonstrate that amphiregulin-producing pathogenic memory Th2 cells control airway fibrosis through the osteopontin produced by inflammatory eosinophils. The identification of this new pathogenic Th cell population supports the concept of “Pathogenic Th population disease induction model”, and will provide novel strategies for treating intractable diseases, including lung fibrosis.

中文翻译：

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肺纤维化的免疫病理学：产生双调蛋白的致病性记忆T helper-2细胞通过诱导嗜酸性粒细胞分泌骨桥蛋白来控制气道纤维化反应。

纤维化被定义为细胞外基质（ECM）在各种器官的实质中的过多沉积，有时会导致不可逆的器官功能障碍，例如特发性肺纤维化（IPF），这是一种致命的肺部疾病。慢性炎症刺激在各种器官中引起纤维化反应。各种免疫细胞，包括肺部的T辅助（Th）细胞，可以保护宿主免受各种有害颗粒（包括病原微生物）的侵害。但是，这些免疫细胞在肺中的功能失调有时会引起炎症性疾病，例如肺纤维化。在这篇综述中，我们将概述肺中致病性纤维化反应的细胞和分子机制。我们还将介绍“致病性Th人群疾病诱导模型”的概念，其中某些Th细胞亚群的独特亚群控制着免疫介导的炎症性疾病的病理。最后，我们介绍了我们最近的发现，这些发现表明，产生双调蛋白的病原性记忆Th2细胞通过炎症性嗜酸性粒细胞产生的骨桥蛋白控制气道纤维化。这种新的致病性Th细胞种群的鉴定支持“致病性Th种群疾病诱导模型”的概念，并将为治疗包括肺纤维化在内的顽固性疾病提供新的策略。证明产生双调蛋白的病原性记忆Th2细胞通过炎症性嗜酸性粒细胞产生的骨桥蛋白控制气道纤维化。对这种新的致病性Th细胞种群的鉴定支持“致病性Th种群疾病诱导模型”的概念，并将为治疗包括肺纤维化在内的顽固性疾病提供新的策略。证明产生双调蛋白的病原性记忆Th2细胞通过炎症性嗜酸性粒细胞产生的骨桥蛋白控制气道纤维化。对这种新的致病性Th细胞种群的鉴定支持“致病性Th种群疾病诱导模型”的概念，并将为治疗包括肺纤维化在内的顽固性疾病提供新的策略。