Recruiting lymphocytes

Abstract

Circulating naive lymphocytes are recruited from the blood to homeostatic lymph nodes (LNs) by the chemokines CCL19 and CCL21, which are ligands for the CCR7 receptor. However, upon infection and inflammation, reactive LNs undergo structural changes and alter their gene expression to facilitate lymphocyte activation. In Cell, Chen et al. examine how inflammation alters the chemotactic signals for LN recruitment of naive lymphocytes. They find that naive lymphocyte recruitment becomes less dependent on CCL21, which undergoes a rapid and persistent downregulation by mouse high-endothelial venules (HEVs) and fibroblastic reticular cells (FRCs) in reactive LNs. By contrast, Ch25h is highly expressed by HEVs and migrating Langerhans cells. Ch25h, together with Cyp7b1 expressed by FRCs, controls the synthesis of the oxysterol ligand for the chemoattractant receptor EBI2 expressed on naive lymphocytes. The authors find that naive B cells are more dependent on this oxysterol–EBI2 axis for recruitment into inflamed LNs, as well as in several tumor models. CCR7⁺ naive and central memory T cells become more dependent on CCL19-mediated recruitment to inflamed LNs. The signals that alter the expression of these chemotactic mediators are unclear, as the authors rule out interferon signaling; however, they point out that chronic downregulation of CCL21 could alter adaptive immune cell responses.

Original reference: Cell https://doi.org/10.1016/j.cell.2024.11.031 (2024)