CSF-1 regulates the function of monocytes in Crohn’s disease patients in remission
Abstract During the flare-ups of Crohn’s disease (CD) patients, circulating leukocytes actively migrate toward the inflamed sites. During the remission, the lack of symptoms does not necessarily imply immunological remission. To decipher inflammatory mechanisms still operating during CD remission, w...
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Format: | Article |
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Nature Portfolio
2017-03-01
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Series: | Scientific Reports |
Online Access: | https://doi.org/10.1038/s41598-017-00145-4 |
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author | Juan Camilo Nieto Carlos Zamora Elisabet Cantó Esther Garcia-Planella Jordi Gordillo Maria Angels Ortiz Cándido Juárez Silvia Vidal |
author_facet | Juan Camilo Nieto Carlos Zamora Elisabet Cantó Esther Garcia-Planella Jordi Gordillo Maria Angels Ortiz Cándido Juárez Silvia Vidal |
author_sort | Juan Camilo Nieto |
collection | DOAJ |
description | Abstract During the flare-ups of Crohn’s disease (CD) patients, circulating leukocytes actively migrate toward the inflamed sites. During the remission, the lack of symptoms does not necessarily imply immunological remission. To decipher inflammatory mechanisms still operating during CD remission, we compared the expression of chemokine receptors on monocytes from CD and healthy donors (HD), and how these differences could modulate monocyte maturation and cytokine production. Flow cytometry analysis showed a higher expression of CCR5 on monocytes from CD patients than those from HD after 24 h. This CCR5 upregulation was associated with the spontaneous production of CSF-1 and IL-10. The higher expression of CCR5 on CD monocytes increased their migratory pattern in response to CCL5. Signaling through CCR5/CCL5 increased CD163 and HLA-DR expression and diminished TLR4-induced TNF-α and IL-6 secretion during monocyte differentiation. When we analyzed clinical parameters, patients treated with azathioprine had the highest CSF-1 levels and CCR5 expression. Our results suggest that monocytes from CD patients in remission produced high levels of CSF-1 that upregulate CCR5 expression. Consequently, monocytes differentiated in these conditions had a characteristic phenotype and lower production of inflammatory cytokines. The treatment with azathioprine could be responsible for this anti-inflammatory profile of monocytes. |
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format | Article |
id | doaj.art-7bcdde80196145a1b3509c248893f0da |
institution | Directory Open Access Journal |
issn | 2045-2322 |
language | English |
last_indexed | 2024-12-19T03:57:46Z |
publishDate | 2017-03-01 |
publisher | Nature Portfolio |
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series | Scientific Reports |
spelling | doaj.art-7bcdde80196145a1b3509c248893f0da2022-12-21T20:36:46ZengNature PortfolioScientific Reports2045-23222017-03-017111110.1038/s41598-017-00145-4CSF-1 regulates the function of monocytes in Crohn’s disease patients in remissionJuan Camilo Nieto0Carlos Zamora1Elisabet Cantó2Esther Garcia-Planella3Jordi Gordillo4Maria Angels Ortiz5Cándido Juárez6Silvia Vidal7Institut Recerca Hospital de la Santa Creu i Sant PauInstitut Recerca Hospital de la Santa Creu i Sant PauInstitut Recerca Hospital de la Santa Creu i Sant PauDepartment of Gastroenterology, Hospital de la Santa Creu i Sant PauDepartment of Gastroenterology, Hospital de la Santa Creu i Sant PauInstitut Recerca Hospital de la Santa Creu i Sant PauInstitut Recerca Hospital de la Santa Creu i Sant PauInstitut Recerca Hospital de la Santa Creu i Sant PauAbstract During the flare-ups of Crohn’s disease (CD) patients, circulating leukocytes actively migrate toward the inflamed sites. During the remission, the lack of symptoms does not necessarily imply immunological remission. To decipher inflammatory mechanisms still operating during CD remission, we compared the expression of chemokine receptors on monocytes from CD and healthy donors (HD), and how these differences could modulate monocyte maturation and cytokine production. Flow cytometry analysis showed a higher expression of CCR5 on monocytes from CD patients than those from HD after 24 h. This CCR5 upregulation was associated with the spontaneous production of CSF-1 and IL-10. The higher expression of CCR5 on CD monocytes increased their migratory pattern in response to CCL5. Signaling through CCR5/CCL5 increased CD163 and HLA-DR expression and diminished TLR4-induced TNF-α and IL-6 secretion during monocyte differentiation. When we analyzed clinical parameters, patients treated with azathioprine had the highest CSF-1 levels and CCR5 expression. Our results suggest that monocytes from CD patients in remission produced high levels of CSF-1 that upregulate CCR5 expression. Consequently, monocytes differentiated in these conditions had a characteristic phenotype and lower production of inflammatory cytokines. The treatment with azathioprine could be responsible for this anti-inflammatory profile of monocytes.https://doi.org/10.1038/s41598-017-00145-4 |
spellingShingle | Juan Camilo Nieto Carlos Zamora Elisabet Cantó Esther Garcia-Planella Jordi Gordillo Maria Angels Ortiz Cándido Juárez Silvia Vidal CSF-1 regulates the function of monocytes in Crohn’s disease patients in remission Scientific Reports |
title | CSF-1 regulates the function of monocytes in Crohn’s disease patients in remission |
title_full | CSF-1 regulates the function of monocytes in Crohn’s disease patients in remission |
title_fullStr | CSF-1 regulates the function of monocytes in Crohn’s disease patients in remission |
title_full_unstemmed | CSF-1 regulates the function of monocytes in Crohn’s disease patients in remission |
title_short | CSF-1 regulates the function of monocytes in Crohn’s disease patients in remission |
title_sort | csf 1 regulates the function of monocytes in crohn s disease patients in remission |
url | https://doi.org/10.1038/s41598-017-00145-4 |
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