The ‘atypical’ chemokine receptor CCRL1 aids dendritic cell migration from inflamed skin. (P6352)

Abstract

Abstract Chemokine-directed leukocyte migration is essential for immune and inflammatory responses. The chemokine receptor CCR7, by responding to chemokines CCL19 and CCL21, is critical in regulating the recruitment of dendritic cells (DC), from peripheral tissues to draining lymph nodes (LNs). CCR7 is required for DC entry into lymphatic vessels, and for the passage of these cells across subcapsular sinus of the lymph node. Here, they initiate adaptive immune responses by priming antigen-specific T cells. CCRL1, an unexpected second receptor for CCL19 and CCL21, belongs to the family of atypical chemokine receptors and is able to bind and sequester extracellular chemokine without exhibiting any form of classical chemokine signaling. CCRL1 function in vivo is still unclear. We have generated CCRL1 deficient mice but find no perturbations in DC numbers in the LNs at rest, and DC trafficking from the skin is normal after painting with hapten (FITC). However, if FITC is applied after the induction of cutaneous inflammation, FITC+ DCs fail to reach draining LNs. Using a combination of microscopy and flow cytometry, we show that DCs are unable to enter lymphatic vessels and remain trapped in the skin. These data will be presented in the context of new insights into the identity of CCRL1-expressing cells in the skin and lymph node. Collectively, our data indicate that CCRL1-mediated regulation of CCL19 and/or CCL21 is required to maintain DC departure from the skin during inflammation.