Amniotic MSCs reduce pulmonary fibrosis by hampering lung B‐cell recruitment, retention, and maturation
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‐ind...
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doaj-b30523ac84ea4b6e9483cd1f060e77a22020-11-25T03:43:34ZengWileyStem Cells Translational Medicine2157-65642157-65802020-09-01991023103510.1002/sctm.20-0068Amniotic MSCs reduce pulmonary fibrosis by hampering lung B‐cell recruitment, retention, and maturationAnna Cargnoni0Pietro Romele1Patrizia Bonassi Signoroni2Serafina Farigu3Marta Magatti4Elsa Vertua5Ivan Toschi6Valentina Cesari7Antonietta R. Silini8Francesca R. Stefani9Ornella Parolini10Centro di Ricerca E Menni, Fondazione Poliambulanza‐Istituto Ospedaliero Brescia ItalyCentro di Ricerca E Menni, Fondazione Poliambulanza‐Istituto Ospedaliero Brescia ItalyCentro di Ricerca E Menni, Fondazione Poliambulanza‐Istituto Ospedaliero Brescia ItalyCentro di Ricerca E Menni, Fondazione Poliambulanza‐Istituto Ospedaliero Brescia ItalyCentro di Ricerca E Menni, Fondazione Poliambulanza‐Istituto Ospedaliero Brescia ItalyCentro di Ricerca E Menni, Fondazione Poliambulanza‐Istituto Ospedaliero Brescia ItalyDip. Scienze Agrarie e Ambientali Università degli Studi di Milano Milan ItalyDip. Scienze Agrarie e Ambientali Università degli Studi di Milano Milan ItalyCentro di Ricerca E Menni, Fondazione Poliambulanza‐Istituto Ospedaliero Brescia ItalyCentro di Ricerca E Menni, Fondazione Poliambulanza‐Istituto Ospedaliero Brescia ItalyCentro di Ricerca E Menni, Fondazione Poliambulanza‐Istituto Ospedaliero Brescia ItalyAbstract 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.https://doi.org/10.1002/sctm.20-0068amniotic mesenchymal stromal cellsB lymphocytesbleomycinlung fibrosis |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Anna Cargnoni Pietro Romele Patrizia Bonassi Signoroni Serafina Farigu Marta Magatti Elsa Vertua Ivan Toschi Valentina Cesari Antonietta R. Silini Francesca R. Stefani Ornella Parolini |
spellingShingle |
Anna Cargnoni Pietro Romele Patrizia Bonassi Signoroni Serafina Farigu Marta Magatti Elsa Vertua Ivan Toschi Valentina Cesari Antonietta R. Silini Francesca R. Stefani Ornella Parolini Amniotic MSCs reduce pulmonary fibrosis by hampering lung B‐cell recruitment, retention, and maturation Stem Cells Translational Medicine amniotic mesenchymal stromal cells B lymphocytes bleomycin lung fibrosis |
author_facet |
Anna Cargnoni Pietro Romele Patrizia Bonassi Signoroni Serafina Farigu Marta Magatti Elsa Vertua Ivan Toschi Valentina Cesari Antonietta R. Silini Francesca R. Stefani Ornella Parolini |
author_sort |
Anna Cargnoni |
title |
Amniotic MSCs reduce pulmonary fibrosis by hampering lung B‐cell recruitment, retention, and maturation |
title_short |
Amniotic MSCs reduce pulmonary fibrosis by hampering lung B‐cell recruitment, retention, and maturation |
title_full |
Amniotic MSCs reduce pulmonary fibrosis by hampering lung B‐cell recruitment, retention, and maturation |
title_fullStr |
Amniotic MSCs reduce pulmonary fibrosis by hampering lung B‐cell recruitment, retention, and maturation |
title_full_unstemmed |
Amniotic MSCs reduce pulmonary fibrosis by hampering lung B‐cell recruitment, retention, and maturation |
title_sort |
amniotic mscs reduce pulmonary fibrosis by hampering lung b‐cell recruitment, retention, and maturation |
publisher |
Wiley |
series |
Stem Cells Translational Medicine |
issn |
2157-6564 2157-6580 |
publishDate |
2020-09-01 |
description |
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. |
topic |
amniotic mesenchymal stromal cells B lymphocytes bleomycin lung fibrosis |
url |
https://doi.org/10.1002/sctm.20-0068 |
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