Polarization of Chemokine Receptors to the Leading Edge during Lymphocyte Chemotaxis

TLDR

Leukocyte chemotaxis, driven by chemokine gradients, is essential for immune surveillance and inflammation, yet the precise molecular mechanism of how chemokines polarize leukocytes remains unclear. The study aimed to determine whether CC chemokine receptors CCR2 and CCR5, but not cytokine receptors, redistribute to a pole in T cells during chemokine‑stimulated migration. Using immunofluorescence and confocal microscopy, the authors visualized that CCR2 and CCR5 accumulate at the leading edge of migrating T cells, a redistribution induced by polarization signals, blocked by pertussis toxin, and requiring integrin‑mediated adhesion. The polarized localization of CCR2 and CCR5 at the leading edge functions as a sensor for directed migration, and their redistribution is G‑protein–dependent and integrin‑dependent, confirming a key role for chemokine receptor polarization in leukocyte chemotaxis.

Abstract

Leukocyte migration in response to cell attractant gradients or chemotaxis is a key phenomenon both in cell movement and in the inflammatory response. Chemokines are quite likely to be the key molecules directing migration of leukocytes that involve cell polarization with generation of specialized cell compartments. The precise mechanism of leukocyte chemoattraction is not known, however. In this study, we demonstrate that the CC chemokine receptors CCR2 and CCR5, but not cytokine receptors such as interleukin (IL)-2Ralpha, IL-2Rbeta, tumor necrosis factor receptor 1, or transforming growth factor betaR, are redistributed to a pole in T cells that are migrating in response to chemokines. Immunofluorescence and confocal microscopy studies show that the chemokine receptors concentrate at the leading edge of the cell on the flattened cell-substratum contact area, induced specifically by the signals that trigger cell polarization. The redistribution of chemokine receptors is blocked by pertussis toxin and is dependent on cell adhesion through integrin receptors, which mediate cell migration. Chemokine receptor expression on the leading edge of migrating polarized lymphocytes appears to act as a sensor mechanism for the directed migration of leukocytes through a chemoattractant gradient.