Augmented concentrations of CX3CL1 are associated with interstitial lung disease in systemic sclerosis.
BACKGROUND:Dysregulation of Fractalkine (CX3CL1) and its receptor CX3CR1 has been linked to the pathobiology of chronic inflammatory conditions. We explored CX3CL1 in systemic sclerosis (SSc) related progressive interstitial lung disease (ILD) and pulmonary hypertension (PH) in two different but com...
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doaj-35807d8610404e829ad34bc846b6ab312020-11-25T02:00:33ZengPublic Library of Science (PLoS)PLoS ONE1932-62032018-01-011311e020654510.1371/journal.pone.0206545Augmented concentrations of CX3CL1 are associated with interstitial lung disease in systemic sclerosis.Anna-Maria Hoffmann-VoldStephen Samuel WeigtVyacheslav PalchevskiyElizabeth VolkmannRajan SaggarNing LiØyvind MidtvedtMay Brit LundTorhild GarenMichael C FishbeinAbbas ArdehaliDavid J RossThor UelandPål AukrustJoseph P LynchRobert M ElashoffØyvind MolbergJohn A BelperioBACKGROUND:Dysregulation of Fractalkine (CX3CL1) and its receptor CX3CR1 has been linked to the pathobiology of chronic inflammatory conditions. We explored CX3CL1 in systemic sclerosis (SSc) related progressive interstitial lung disease (ILD) and pulmonary hypertension (PH) in two different but complementary sources of biomaterial. METHODS:We collected lung tissue at the time of lung transplantation at UCLA from SSc-ILD patients (n = 12) and healthy donors (n = 12); and serum samples from the prospective Oslo University Hospital SSc cohort (n = 292) and healthy donors (n = 100). CX3CL1 was measured by ELISA. Cellular sources of CX3CL1/CX3CR1 in lung tissues were determined by immunohistochemistry and immunofluorescence. ILD progression and new onset PH endpoints were analysed. RESULTS:CX3CL1 concentrations were increased in SSc in lung tissue as well as in sera. In the UCLA cohort, CX3CL1 was highly correlated with DLCO. In the SSc-ILD lungs, CX3CL1 was identified in reactive type II pneumocytes and airway epithelial cells. CX3CR1 stained infiltrating interstitial mononuclear cells, especially plasma cells. In the Oslo cohort, CX3CL1 correlated with anti-Topoisomerase-I-antibody and lung fibrosis. CX3CL1 was associated with ILD progression in multivariable regression analysis but not PH. CONCLUSION:CX3CL1 is associated with progressive SSc-ILD but not SSc-PH. The CX3CR1/CX3CL1-biological axis may be involved in recruiting antibody secreting plasma cells to SSc lungs, thereby contributing to the immune-mediated pathobiology of SSc-ILD.http://europepmc.org/articles/PMC6245508?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Anna-Maria Hoffmann-Vold Stephen Samuel Weigt Vyacheslav Palchevskiy Elizabeth Volkmann Rajan Saggar Ning Li Øyvind Midtvedt May Brit Lund Torhild Garen Michael C Fishbein Abbas Ardehali David J Ross Thor Ueland Pål Aukrust Joseph P Lynch Robert M Elashoff Øyvind Molberg John A Belperio |
spellingShingle |
Anna-Maria Hoffmann-Vold Stephen Samuel Weigt Vyacheslav Palchevskiy Elizabeth Volkmann Rajan Saggar Ning Li Øyvind Midtvedt May Brit Lund Torhild Garen Michael C Fishbein Abbas Ardehali David J Ross Thor Ueland Pål Aukrust Joseph P Lynch Robert M Elashoff Øyvind Molberg John A Belperio Augmented concentrations of CX3CL1 are associated with interstitial lung disease in systemic sclerosis. PLoS ONE |
author_facet |
Anna-Maria Hoffmann-Vold Stephen Samuel Weigt Vyacheslav Palchevskiy Elizabeth Volkmann Rajan Saggar Ning Li Øyvind Midtvedt May Brit Lund Torhild Garen Michael C Fishbein Abbas Ardehali David J Ross Thor Ueland Pål Aukrust Joseph P Lynch Robert M Elashoff Øyvind Molberg John A Belperio |
author_sort |
Anna-Maria Hoffmann-Vold |
title |
Augmented concentrations of CX3CL1 are associated with interstitial lung disease in systemic sclerosis. |
title_short |
Augmented concentrations of CX3CL1 are associated with interstitial lung disease in systemic sclerosis. |
title_full |
Augmented concentrations of CX3CL1 are associated with interstitial lung disease in systemic sclerosis. |
title_fullStr |
Augmented concentrations of CX3CL1 are associated with interstitial lung disease in systemic sclerosis. |
title_full_unstemmed |
Augmented concentrations of CX3CL1 are associated with interstitial lung disease in systemic sclerosis. |
title_sort |
augmented concentrations of cx3cl1 are associated with interstitial lung disease in systemic sclerosis. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2018-01-01 |
description |
BACKGROUND:Dysregulation of Fractalkine (CX3CL1) and its receptor CX3CR1 has been linked to the pathobiology of chronic inflammatory conditions. We explored CX3CL1 in systemic sclerosis (SSc) related progressive interstitial lung disease (ILD) and pulmonary hypertension (PH) in two different but complementary sources of biomaterial. METHODS:We collected lung tissue at the time of lung transplantation at UCLA from SSc-ILD patients (n = 12) and healthy donors (n = 12); and serum samples from the prospective Oslo University Hospital SSc cohort (n = 292) and healthy donors (n = 100). CX3CL1 was measured by ELISA. Cellular sources of CX3CL1/CX3CR1 in lung tissues were determined by immunohistochemistry and immunofluorescence. ILD progression and new onset PH endpoints were analysed. RESULTS:CX3CL1 concentrations were increased in SSc in lung tissue as well as in sera. In the UCLA cohort, CX3CL1 was highly correlated with DLCO. In the SSc-ILD lungs, CX3CL1 was identified in reactive type II pneumocytes and airway epithelial cells. CX3CR1 stained infiltrating interstitial mononuclear cells, especially plasma cells. In the Oslo cohort, CX3CL1 correlated with anti-Topoisomerase-I-antibody and lung fibrosis. CX3CL1 was associated with ILD progression in multivariable regression analysis but not PH. CONCLUSION:CX3CL1 is associated with progressive SSc-ILD but not SSc-PH. The CX3CR1/CX3CL1-biological axis may be involved in recruiting antibody secreting plasma cells to SSc lungs, thereby contributing to the immune-mediated pathobiology of SSc-ILD. |
url |
http://europepmc.org/articles/PMC6245508?pdf=render |
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