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.
Highlights
Crohn’s disease (CD) is a disorder of the gastrointestinal mucosa, characterized by the infiltration of immune cells into the lamina propria
Our findings showed a higher CCR5 upregulation on CD monocytes than on healthy donors (HD) monocytes induced by a higher CSF-1 and IL-10 production in CD than in HD cultures
The migratory pattern and the maturation status in CD monocytes were different from HD monocytes
Summary
Crohn’s disease (CD) is a disorder of the gastrointestinal mucosa, characterized by the infiltration of immune cells into the lamina propria. During the maturation into tissue macrophages, monocytes are accompanied by a loss of CCR2 and an increased expression of CCR1 and CCR56, 7 These chemokine receptor switches on the monocyte might indicate that the CCL2/CCR2 axis is involved in the initial recruitment, followed by a subsequent CCR5/CCL5-dependent migration into the tissues[8]. This different profile of chemokine receptors could modulate their migratory pattern, and the monocyte maturation and cytokine response For this purpose, we assessed peripheral blood monocytes from CD patients in remission, their chemokine receptors expression (CCR2, CCR5, CXCR4 and CX3CR1), migratory capacity, the influence of chemokines during monocyte maturation and cytokine production, and their relationship with clinical parameters and the development of the disease
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