Amniotic MSCs reduce pulmonary fibrosis by hampering lung B‐cell recruitment, retention, and maturation

Stem Cells Translational Medicine

Francesca R. Stefani¹  Serafina Farigu¹  Antonietta R. Silini¹  Pietro Romele¹  Ornella Parolini¹  Patrizia Bonassi Signoroni¹  Elsa Vertua¹  Anna Cargnoni¹  Marta Magatti¹  Ivan Toschi²  Valentina Cesari² 

[1] Centro di Ricerca E Menni, Fondazione Poliambulanza‐Istituto Ospedaliero Brescia Italy;Dip. Scienze Agrarie e Ambientali Università degli Studi di Milano Milan Italy;

关键词: amniotic mesenchymal stromal cells;    B lymphocytes;    bleomycin;    lung fibrosis;   

DOI  :  10.1002/sctm.20-0068

来源: DOAJ

【 摘 要 】

Abstract 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.

【 授权许可】

Unknown