Open AccessCSF-1 regulates the function of monocytes in Crohn’s disease patients in remission
Author(s) -
Juan C. Nieto,
Carlos Zamora,
Elisabet Cantó,
Esther GarcíaPlanella,
Jordi Gordillo,
Michele Purper Ortiz,
Cándido Júarez,
Sílvia Vidal
Publication year - 2017
Publication title -
scientific reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.24
H-Index - 213
ISSN - 2045-2322
DOI - 10.1038/s41598-017-00145-4
Subject(s) - chemokine , monocyte , immunology , cd163 , ccl5 , downregulation and upregulation , azathioprine , crohn's disease , cytokine , medicine , flow cytometry , receptor , biology , inflammation , il 2 receptor , disease , t cell , immune system , macrophage , in vitro , biochemistry , gene
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.