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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Main Authors: Juan Camilo Nieto, Carlos Zamora, Elisabet Cantó, Esther Garcia-Planella, Jordi Gordillo, Maria Angels Ortiz, Cándido Juárez, Silvia Vidal
Format: Article
Language:English
Published: Nature Portfolio 2017-03-01
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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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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