Role of C-C chemokine receptor type 7 and its ligands during neuroinflammation

For decades, chemokines and their receptors have received a great deal of attention for their multiple roles in controlling leukocyte functions during inflammation and immunity. The ability of chemokines to convey remarkably versatile but context-specific signals identifies them as powerful modulators of immune responses generated in response to diverse pathogenic or non-infectious insults. A number of recent studies have speculated that the C-C chemokine receptor type 7 (CCR7), plays important roles in immune-cell trafficking in various tissue compartments during inflammation and in immune surveillance. Using computational modeling and microfluidics-based approaches, recent studies have explored leukocyte migration behavior in response to CCR7 ligands in a complex chemokine environment existing with other coexisting chemokine fields. In this review, we summarize the current understanding of the effects of soluble versus immobilized ligands and of the downstream signaling pathways of CCR7 that control leukocyte motility, directionality, and speed. This review also integrates the current knowledge about the role of CCR7 in coordinating immune responses between secondary lymphoid organs and peripheral tissue microenvironments during primary or secondary antigen encounters. CCR7 seems to influence distinct immunological events during inflammatory responses in the central nervous system (CNS) including immune-cell entry and migration, and neuroglial interactions. The clinical and pathological outcome may vary depending on its contribution in the inflamed CNS microenvironment. Understanding these mechanisms has direct implications for therapeutic developments favoring more protective and efficient immune responses.