Regulatory T Cells Limit Pneumococcus-Induced Exacerbation of Lung Fibrosis in Mice
Regulatory T Cells Limit Pneumococcus-Induced Exacerbation of Lung Fibrosis in Mice
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DOI：
10.4049/jimmunol.1900980
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发表时间：
2020-05-01
影响因子：
4.4
通讯作者：
Maus, Ulrich A.
中科院分区：
文献类型：
--
作者：
Moye, Steffi;Bormann, Tina;Maus, Ulrich A.
特发性肺纤维化（IPF）患者可能会发生危及生命的疾病急性恶化，称为IPF急性加重，可能由细菌和/或病毒感染引起。调节性T细胞（TCFs）限制细菌引发的纤维化恶化中疾病进展的潜力迄今尚未探索。在目前的研究中，我们发现，TcB的数量显着增加，在小鼠建立AdTGF-β 1诱导的肺纤维化和进一步增加，在小鼠肺炎球菌感染诱导的肺纤维化恶化。白喉毒素诱导的Tcl 4耗竭显著恶化了感染诱导的纤维化恶化，如通过增加的肺胶原沉积、肺组织学和升高的肺Th 1/Th 2细胞因子水平所确定的。相反，IL-2复合物诱导的Treg扩增在具有已建立的肺纤维化的野生型小鼠中完全抑制肺炎球菌感染诱导的纤维化恶化，与抗生素治疗一样有效，同时保留小鼠中的肺抗菌免疫。总的来说，这些发现证明了TIFE作为“沉默剂”的疗效，抑制小鼠感染诱导的肺纤维化加重，其扩展可能提供一种新的预防性治疗，以限制IPF患者的急性加重。
Patients with idiopathic pulmonary fibrosis (IPF) can experience life-threatening episodes of acute worsening of their disease, termed acute exacerbation of IPF, which may be caused by bacterial and/or viral infections. The potential for regulatory T cells (Tregs) to limit disease progression in bacterially triggered fibrosis exacerbation has not been explored so far. In the current study, we show that the number of Tregs was significantly increased in mice with established AdTGF-beta 1-induced lung fibrosis and further increased in mice with pneumococcal infection-induced lung fibrosis exacerbation. Diphtheria toxin-induced depletion of Tregs significantly worsened infection-induced fibrosis exacerbation as determined by increased lung collagen deposition, lung histology, and elevated pulmonary Th1/Th2 cytokine levels. Conversely, IL-2 complex-induced Treg expansion in wild-type mice with established lung fibrosis completely inhibited pneumococcal infection-induced fibrosis exacerbation as efficaciously as antibiotic treatment while preserving lung antibacterial immunity in mice. Collectively, these findings demonstrate the efficacy of Tregs as "silencers," suppressing infection-induced exacerbation of lung fibrosis in mice, and their expansion may offer a novel adjunctive treatment to limit acute exacerbations in patients with IPF.