Signal Relay by CC Chemokine Receptor 2 (CCR2) and Formylpeptide Receptor 2 (Fpr2) in the Recruitment of Monocyte-derived Dendritic Cells in Allergic Airway Inflammation*

Chemoattractant receptors regulate leukocyte accumulation at sites of inflammation. In allergic airway inflammation, although a chemokine receptor CCR2 was implicated in mediating monocyte-derived dendritic cell (DC) recruitment into the lung, we previously also discovered reduced accumulation of DCs in the inflamed lung in mice deficient in formylpeptide receptor Fpr2 (Fpr2^−/−). We therefore investigated the role of Fpr2 in the trafficking of monocyte-derived DCs in allergic airway inflammation in cooperation with CCR2. We report that in allergic airway inflammation, CCR2 mediated the recruitment of monocyte-derived DCs to the perivascular region, and Fpr2 was required for further migration of the cells into the bronchiolar area. We additionally found that the bronchoalveolar lavage liquid from mice with airway inflammation contained both the CCR2 ligand CCL2 and an Fpr2 agonist CRAMP. Furthermore, similar to Fpr2^−/− mice, in the inflamed airway of CRAMP^−/− mice, DC trafficking into the peribronchiolar areas was diminished. Our study demonstrates that the interaction of CCR2 and Fpr2 with their endogenous ligands sequentially mediates the trafficking of DCs within the inflamed lung.

Background: Chemoattractant receptor Fpr2 interacts with host-derived agonists and mediates leukocyte trafficking.

Results: In the lung of allergic inflammation, chemokine receptor CCR2 elicits accumulation of monocyte-derived DC in perivascular region, but Fpr2 is critical for cell trafficking to peribronchiolar area.

Conclusion: CCR2 and Fpr2 sequentially guide DC trafficking in inflamed lung.

Significance: DC trafficking is controlled by multiple chemoattractant receptors, which are potential therapeutic targets.