Department of Hematology, Oncology, Allergy and Respiratory Medicine, Okayama University Academic Field of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan.
Department of Allergy and Respiratory Medicine, Okayama University Hospital, Okayama, Japan.
Respir Investig. 2023 Sep;61(5):553-562. doi: 10.1016/j.resinv.2023.05.005. Epub 2023 Jun 23.
Fibrosis of the lung can occur in idiopathic pulmonary fibrosis, collagen vascular diseases, and hypersensitivity pneumonitis, among other diseases. Transforming growth factor (TGF)-β, vascular epithelial growth factor, fibroblast growth factor, and platelet-derived growth factor contribute to the pathophysiology of fibrosis. TGF-β and other cytokines, including interleukin (IL)-1β, IL-6, and IL-23, activate type-17 immunity, which is involved in pulmonary fibrosis. The components of type-17 immunity include type-17 helper T cells, γδT cells, IL-17A-producing CD8-positive T cells, invariant NKT cells, and group 3 innate lymphoid cells. IL-17A, the main cytokine of type-17 immunity, is able to induce the epithelial-mesenchymal transition in epithelial cells via a production of TGF-β, directly stimulate fibroblasts and fibrocytes, and inhibit autophagy, which otherwise protects against pulmonary fibrosis. IL-23 induces type-17 immunity and plays an important role in the acute exacerbation of pulmonary fibrosis. Clinical studies have also linked type-17 immunity to the pathogenesis of pulmonary fibrosis. Consequently, targeting type-17 immunity may serve as a new therapeutic strategy to prevent the development or exacerbation of pulmonary fibrosis.
肺纤维化可发生于特发性肺纤维化、胶原血管疾病和过敏性肺炎等疾病中。转化生长因子（TGF）-β、血管上皮生长因子、成纤维细胞生长因子和血小板衍生生长因子有助于纤维化的病理生理学。TGF-β和其他细胞因子，包括白细胞介素（IL）-1β、IL-6 和 IL-23，激活 17 型免疫，该免疫与肺纤维化有关。17 型免疫的组成部分包括 17 型辅助 T 细胞、γδT 细胞、产生 IL-17A 的 CD8阳性 T 细胞、不变自然杀伤 T 细胞和第 3 组先天淋巴细胞。17 型免疫的主要细胞因子 IL-17A 能够通过 TGF-β的产生诱导上皮细胞的上皮-间充质转化，直接刺激成纤维细胞和纤维细胞，并抑制自噬，而自噬可防止肺纤维化。IL-23 诱导 17 型免疫，并在肺纤维化的急性加重中发挥重要作用。临床研究也将 17 型免疫与肺纤维化的发病机制联系起来。因此，针对 17 型免疫可能成为预防肺纤维化发展或加重的新治疗策略。
