Louvain Centre for Toxicology and Applied Pharmacology (LTAP), Institut de Recherche Experimentale et Clinique (IREC), Université Catholique de Louvain, Brussels, Belgium.
Front Immunol. 2021 Aug 20;12:690375. doi: 10.3389/fimmu.2021.690375. eCollection 2021.
Immunostimulation is recognized as an important contribution in lung fibrosis in some animal models and patient subsets. With this review, we illustrate an additional scenario covering the possible implication of immunoregulation during fibrogenesis. Available animal and human data indicate that pulmonary fibrosis also includes diverse and discrete immunoregulating populations comprising regulatory lymphocytes (T and B regs) and myeloid cells (immunosuppressive macrophages and myeloid-derived suppressive cells; MDSC). They are initially recruited to limit the establishment of deleterious inflammation but participate in the development of lung fibrosis by producing immunoregulatory mediators (mainly TGF-β1 and IL-10) that directly or indirectly stimulate fibroblasts and matrix protein deposition. The existence of this silent immunoregulatory environment sustains an alternative mechanism of fibrosis that explains why in some conditions neither pro-inflammatory cytokine deficiency nor steroid and immunosuppressive therapies limit lung fibrosis. Therefore, the persistent presence of immunoregulation is an important parameter to consider for refining therapeutical strategies in lung fibrotic disorders under non-immunostimulatory conditions.
免疫刺激被认为是某些动物模型和患者亚群中肺纤维化的一个重要贡献。通过本次综述，我们展示了一个涵盖纤维化过程中免疫调节可能影响的附加情况。现有的动物和人类数据表明，肺纤维化还包括多种不同的免疫调节群体，包括调节性淋巴细胞（T 和 B regs）和髓样细胞（免疫抑制性巨噬细胞和髓源性抑制细胞；MDSC）。它们最初被招募来限制有害炎症的建立，但通过产生免疫调节介质（主要是 TGF-β1 和 IL-10）来参与肺纤维化的发展，这些介质直接或间接地刺激成纤维细胞和基质蛋白沉积。这种沉默的免疫调节环境的存在维持了纤维化的另一种机制，解释了为什么在某些情况下，促炎细胞因子缺乏、类固醇和免疫抑制治疗并不能限制肺纤维化。因此，免疫调节的持续存在是在非免疫刺激条件下细化肺纤维化疾病治疗策略的一个重要参数。
