Chemokine positioning assists extravasation of pathogenic human T cells

Th17 lymphocytes have well established roles in immune responses to extracellular bacteria and fungal pathogens, with their cytokines participating in wound repair and neutrophil activation. While CCR6 expression on Th17 cells is known, preprint work from Joshua Farber and colleagues at the Laboratory of Molecular Immunology, National Institute of Allergy and Infectious Diseases has uncovered an important role for the receptor CCR2 in assisting in Th17 recruitment. They showed that the CCR6 ligand CCL20 slowed the speed of circulating Th17 cells while the CCR2 ligand CCL2 enhanced the ability of those lymphocytes to squeeze between endothelial cells of the blood vessel wall. Interestingly chemokines like CCL20 were able to form stable interactions within blood vessels, while other ligands unable to form those bonds promoted transendothelial migration. These exciting findings suggest that immune cell trafficking is not simply a binary choice between a single ligand and receptor and requires cooperative interactions to fine tune the movement of lymphocytes into sites of infection.

Chemokine positioning determines mutually exclusive roles for their receptors in extravasation of pathogenic human T cells [bioRxiv. 2023 Feb 13;2023.01.25.525561. doi: 10.1101/2023.01.25.525561.]

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