The greater chemotactic network for lymphocyte trafficking: chemokines and beyond

This review examines our current understanding of the chemoattractant network for lymphocyte trafficking and discusses the recent findings in this area.

The universe of chemoattractants is expanding. Although the approximately 40 chemokines by themselves provide an extensive network of chemotactic signals, it is now clear that nonchemokine molecules such as lipid mediators, pathogen-derived products, antimicrobial peptides, complement products, and other normal constituents of our body are also chemotactic and regulate lymphocyte trafficking. The past several years has witnessed important progress in the area of lymphocyte trafficking: CD45+CD4+CD3- lymphoid tissue inducer cells express CXCR5 and CCR7 and migrate toward lymphoid tissue--organizing stromal cells. Sphingosine 1-phosphate and homeostatic chemokines regulate lymphocyte localization in lymph nodes and egress to circulation. Upon antigen priming, regulatory T cells rapidly upregulate CXCR5 to migrate and suppress germinal center T and B cells. Plasmacytoid dendritic cells can migrate to lymph nodes through high endothelial venule cells, and chemokines and nonchemokine G-protein--coupled seven-transmembrane domain receptor ligands such as chemerin can regulate pDC migration. Gut dendritic cells and retinoic acid induce the expression of alpha4beta7 and CCR9 on T cells for their homing to the gut. Leukotriene B4 and interleukin-8, known chemoattractants for myeloid cells, are also selective chemoattractants for cytotoxic effector T cells.

Immune cells migrate within the vast and dense network of chemoattractants. This greater chemotactic network comprehensively controls lymphoid organogenesis, homeostatic immune cell migration, and effector cell dispatch to clear pathogens.