肺纖維化是一種慢性漸進式發炎疾病並伴隨著高死亡率，近來其好發率也持續攀升。而引起肺纖維化的原因很多，包括吸煙，藥物，衰老，遺傳缺陷和環境因素等。當前大流行的新型冠狀病毒（2019-nCoV）的感染也會導致患者肺纖維化。異常進行組織修復與發炎所引起的肺部細胞外基質堆積是常見的臨床病徵，從而導致肺功能障礙。迄今為止，尚無有效的藥物可以治療肺纖維化。因此，探索肺纖維化的詳細致病機轉對藥物開發具有重要意義。介白素-24與介白素-20共用相同的接收器複合物，包括IL-20R1 / IL-20R2和IL-22R1 / IL-20R2，以執行其生物功能。先前，IL-24被認為是一重要的多功能免疫調節細胞因子。在這項研究中，我們旨在探討IL-24是否參與在發炎引起的肺纖維化病程之中。透過bleomycin所誘導的肺纖維化小鼠模式分析，我們發現給予重組IL-24蛋白能夠有效地保護小鼠免於肺纖維化。進一步我們經由in vitro實驗探討其分子機制。根據實驗結果，我們提出IL-24能夠治療肺纖維化的三條可能路徑。其一，藉由抑制肺泡上皮細胞產生相關促纖維化因子，並阻止其透過EMT機制轉化為成纖維母細胞。其二，抑制肺泡組織間M2巨噬細胞之浸潤，但其分子機制仍需進一步深入探討。其三，透過抑制肺臟中CD4+ T細胞PD-1的表達，並且經由調控轉錄因子NFATc1進而達到抑制PD-1的表現。我們認為IL-24在未來有可能可以作為一潛力藥物來治療肺纖維化。

Pulmonary fibrosis is a chronic and progressive inflammatory disease with the high mortality rate and its incidence continues to rise recently. There are many risk factors for pulmonary fibrosis, including smoking, drugs, aging, genetic defects and environmental factors. Current pandemic infection of the new type coronavirus (2019-nCoV) also caused pulmonary fibrosis in patients. Accumulation of extracellular matrix (ECM) in the lung caused by abnormal tissue repair and the inflammation is the common clinical outcome, leading to pulmonary dysfunction. Up to now, there is no effective drug for treating pulmonary fibrosis. Therefore, it is important to explore the detailed pathogenic mechanism of pulmonary fibrosis for drug development. Interleukin-24 (IL-24) shares the same receptor complexes with IL-20, including IL-20R1/IL-20R2 and IL-22R1/IL-20R2, to perform biological functions. Previously, IL-24 was considered to be an important pleiotropic immune-regulatory cytokine. In this study, we are aimed to investigate whether IL-24 is involved in the progression of pulmonary fibrosis. By analyzing bleomycin-induced mice model, we showed that administration of recombinant IL-24 could effectively protect mice from pulmonary fibrosis. We further explored the molecular mechanism through in vitro experiments. Based on the results, we proposed three possible pathways by which IL-24 protects against pulmonary fibrosis. First, IL-24 inhibits production of profibrogenic factors by alveolar epithelial cells and prevents EMT process. Second, the infiltration of M2 macrophages was blocked by IL-24 treatment. However its molecular mechanism still needs further investigation. Third, IL-24 regulates the transcription factor NFATc1 to suppress the expression of PD-1 on CD4+ T cells in the lung. We conclude that IL-24 may be a potential drug to treat pulmonary fibrosis in the future.

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