Antifibrotics Modify B-Cell-induced Fibroblast Migration and Activation in Patients with Idiopathic Pulmonary Fibrosis
Antifibrotics Modify B-Cell-induced Fibroblast Migration and Activation in Patients with Idiopathic Pulmonary Fibrosis
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DOI：
10.1165/rcmb.2020-0387oc
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发表时间：
2021-06-01
影响因子：
6.4
通讯作者：
Carmona, Eva M.
中科院分区：
文献类型：
--
作者：
Ali, Mohamed F.;Egan, Ashley M.;Carmona, Eva M.
b细胞活化越来越多地与许多纤维化肺部疾病联系在一起，众所周知，在许多这些患者的肺部形成淋巴细胞聚集。模式识别受体（PRRs）激活b细胞，驱动炎症细胞因子、趋化因子和金属蛋白酶的释放，这些在肺纤维化的病理生理中很重要。然而，特发性肺纤维化（IPF）患者b细胞活化的具体机制尚不清楚。在这里，我们已经证明了微生物抗原激活的b细胞有助于IPF患者的炎症和纤维化环境。CpG和β -葡聚糖通过PRRs刺激b细胞导致mtor依赖和独立通路的激活。此外，我们发现b细胞分泌的炎症环境对诱导抗原是特异性的，并导致成纤维细胞的差异迁移和激活。b细胞对感染因子的反应和随后的b细胞介导的成纤维细胞活化可以被抗纤维化药物改变，但每一种似乎都发挥着特定的不同作用。这些结果表明，在PRR被微生物抗原激活后，b细胞可以促进IPF患者的炎症和纤维化变化，而抗纤维化药物至少能够部分逆转这些反应。
B-cell activation is increasingly linked to numerous fibrotic lung diseases, and it is well known that aggregates of lymphocytes form in the lung of many of these patients. Activation of B-cells by pattern recognition receptors (PRRs) drives the release of inflammatory cytokines, chemokines, and metalloproteases important in the pathophysiology of pulmonary fibrosis. However, the specific mechanisms of B-cell activation in patients with idiopathic pulmonary fibrosis (IPF) are poorly understood. Herein, we have demonstrated that B-cell activation by microbial antigens contributes to the inflammatory and profibrotic milieu seen in patients with IPF. B-cell stimulation by CpG and beta-glucan via PRRs resulted in activation of mTOR-dependent and independent pathways. Moreover, we showed that the B-cell-secreted inflammatory milieu is specific to the inducing antigen and causes differential fibroblast migration and activation. B-cell responses to infectious agents and subsequent B-cell-mediated fibroblast activation are modifiable by antifibrotics, but each seems to exert a specific and different effect. These results suggest that, upon PRR activation by microbial antigens, B-cells can contribute to the inflammatory and fibrotic changes seen in patients with IPF, and antifibrotics are able to at least partially reverse these responses.