Related Experiment Video
Updated: Jul 17, 2026
Induction of Experimental Autoimmune Encephalomyelitis in Mice and Evaluation of the Disease-dependent Distribution of Immune Cells in Various Tissues
Published on: May 8, 2016
CCR5 expression on monocytes and T cells: modulation by transmigration across the blood-brain barrier in vitro
Eroboghene E Ubogu1, Melissa K Callahan, Barbara H Tucky
1Neuroinflammation Research Center, Department of Neurosciences, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH 44195, USA.
Abstract:
Observational studies in multiple sclerosis (MS) demonstrated altered expression of chemokine receptors (CkRs) on comparable populations of mononuclear cells (e.g. CD4(+)/CD45RO(+) T-cells) in brain sections compared with blood. These findings raised questions about the regulation of CkRs on trafficking cells. Regulatory processes for CkRs are complex: examples include down-regulation following ligand engagement during migration and either up- or down-regulation following activation. Additionally, CkRs that mediate transmigration without being down-regulated will be selectively enriched on migrating cells in the inflammatory site. Finally, CkRs may act as functionally neutral markers of activated cells capable of undergoing transmigration. Clarifying CkR regulation may aid in the selection and application of antagonists for treating neuroinflammation. Mechanisms of receptor regulation during transmigration cannot be studied by descriptive methods. We evaluated CCR5 expression on CD14(+) monocytes and CD3(+) T-cells following CCL5-driven transmigration through an in vitro blood-brain barrier (IVBBB), as both T-cells and monocytes in MS lesions express CCR5. CCR5 expression was augmented on non-migrating CD14(+) but not CD3(+) cells, suggesting selective activation of monocytes by incubation in contact with endothelial cells. As proposed from observational studies, CCR5 was enriched on monocytes that migrated spontaneously in the absence of exogenous chemokine. Addition of the CCR5 ligand CCL5 to the lower chamber led to enhanced CD3(+) T-cell migration. Interestingly, CCR5 was down-regulated on both CD14(+) monocytes and CD3(+) T cells during CCL5-driven migration. These results are distinct from those obtained in comparable studies of CCR2 and CXCR3, suggesting that the specifics for CkR expression should be studied for individual receptors on each leukocyte subpopulation during the design of strategies for pharmacological blockade in neuroinflammation.
Insights
Chemokine receptor (CkR) regulation in multiple sclerosis (MS) is complex. This study found CCR5 is down-regulated on migrating T-cells and monocytes, informing neuroinflammation treatment strategies.
Area of Science:
- Neuroimmunology
- Cellular and Molecular Immunology
Background:
- Observational studies in multiple sclerosis (MS) show altered chemokine receptor (CkR) expression on immune cells in the brain compared to blood.
- This suggests complex regulation of CkRs on immune cells during trafficking, impacting neuroinflammation.
Purpose of the Study:
- To investigate the regulation of C-C chemokine receptor type 5 (CCR5) on monocytes and T-cells during transmigration across an in vitro blood-brain barrier (IVBBB).
- To understand how CCR5 expression changes on specific leukocyte subpopulations during migration, informing therapeutic strategies for neuroinflammation.
Main Methods:
- Monocytes (CD14+) and T-cells (CD3+) were subjected to CCL5-driven transmigration across an IVBBB model.
- CCR5 expression was analyzed on both migrating and non-migrating cells using flow cytometry.
- CCR5 expression was compared between CD14+ monocytes and CD3+ T-cells.
Main Results:
- CCR5 expression was augmented on non-migrating CD14+ monocytes but not on CD3+ T-cells, indicating selective monocyte activation.
- CCR5 was enriched on spontaneously migrating monocytes.
- CCL5-induced migration of CD3+ T-cells showed CCR5 down-regulation on both monocytes and T-cells.
Conclusions:
- CCR5 regulation differs between leukocyte subpopulations and migration conditions, with down-regulation observed during CCL5-driven migration.
- Findings contrast with CCR2 and CXCR3 regulation, emphasizing the need for receptor-specific studies in neuroinflammation.
- Understanding individual CkR regulation is crucial for designing effective pharmacological blockade strategies in neuroinflammatory diseases.
