Amniotic MSCs reduce pulmonary fibrosis by hampering lung B-cell recruitment, retention, and maturation
Amniotic MSCs reduce pulmonary fibrosis by hampering lung B-cell recruitment, retention, and maturation
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羊水间充质干细胞通过阻碍肺部B细胞的募集、滞留和成熟来减轻肺纤维化
DOI：
10.1002/sctm.20-0068
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发表时间：
2020-05-26
影响因子：
6
通讯作者：
Parolini, Ornella
中科院分区：
文献类型：
--
作者：
Cargnoni, Anna;Romele, Pietro;Parolini, Ornella
越来越多的证据表明炎症与纤维化过程的发展和进展之间存在机械联系。来源于人羊膜的间充质基质细胞（hAMSC）显示出显著的免疫调节特性，已被证明可以减少博来霉素诱导的小鼠肺纤维化，这可能是通过创建能够限制慢性炎症演变为纤维化的微环境。然而，hAMSC调节博来霉素诱导的肺部炎症中涉及的免疫细胞的能力尚未阐明。在此，我们进行了一项关于博来霉素激发后hAMSC对肺泡和肺免疫细胞群的影响的纵向研究。通过支气管肺泡灌洗收集的免疫细胞通过流式细胞术进行检测，并使用肺组织来研究与不同免疫细胞类型相关的标志物的基因表达。我们观察到hAMSC增加了T调节细胞标志物Foxp3的肺表达，增加了巨噬细胞向抗炎表型（M2）的极化，并降低了巨噬细胞和树突状细胞的抗原呈递潜力。我们首次证明了hAMSC显著减少了肺B细胞的募集、保留和成熟，并抵消了肺内淋巴聚集体的形成和扩张。因此，hAMSC可能阻碍由B细胞促进的自我维持的炎性病症，所述B细胞持续充当受损肺中近端T淋巴细胞的抗原呈递细胞。通过调节B细胞反应，hAMSC可能有助于减缓肺部炎症过程的慢性化，从而减少纤维化病变的进展。
Growing evidence suggests a mechanistic link between inflammation and the development and progression of fibrotic processes. Mesenchymal stromal cells derived from the human amniotic membrane (hAMSCs), which display marked immunomodulatory properties, have been shown to reduce bleomycin-induced lung fibrosis in mice, possibly by creating a microenvironment able to limit the evolution of chronic inflammation to fibrosis. However, the ability of hAMSCs to modulate immune cells involved in bleomycin-induced pulmonary inflammation has yet to be elucidated. Herein, we conducted a longitudinal study of the effects of hAMSCs on alveolar and lung immune cell populations upon bleomycin challenge. Immune cells collected through bronchoalveolar lavage were examined by flow cytometry, and lung tissues were used to study gene expression of markers associated with different immune cell types. We observed that hAMSCs increased lung expression of T regulatory cell marker Foxp3, increased macrophage polarization toward an anti-inflammatory phenotype (M2), and reduced the antigen-presentation potential of macrophages and dendritic cells. For the first time, we demonstrate that hAMSCs markedly reduce pulmonary B-cell recruitment, retention, and maturation, and counteract the formation and expansion of intrapulmonary lymphoid aggregates. Thus, hAMSCs may hamper the self-maintaining inflammatory condition promoted by B cells that continuously act as antigen presenting cells for proximal T lymphocytes in injured lungs. By modulating B-cell response, hAMSCs may contribute to blunting of the chronicization of lung inflammatory processes with a consequent reduction of the progression of the fibrotic lesion.