Endothelial Atypical Receptors for Chemoattractants in Lung Immune Surveillance

Chemokines and their receptors play a pivotal role in the initiation and regulation of inflammation through the orchestration of leukocyte extravasation and directed migration toward sites of tissue injury. Tight control of chemokine gradients within tissues is essential to ensure that inflammatory responses remain transient and properly resolved. When this regulatory mechanism fails, dysregulated chemokine signaling can contribute to the development of chronic inflammation. Atypical receptors for chemoattractants comprise atypical chemokine receptors (ACKRs) and the chemerin-presenting receptor CCRL2. ACKRs perform specialized functions enabling the fine-tuning of chemokine gradients, primarily through the scavenging, sequestration, or redistribution of chemokines. By regulating their spatial and temporal availability, ACKRs play a key role in limiting excessive leukocyte recruitment and promoting inflammation resolution. The lungs are in a dynamic equilibrium between immune activation and homeostasis. Rapid and tightly regulated immune cell recruitment is essential for effective host defense while preventing tissue damage. In this context, ACKRs expressed by specialized lung endothelial cells are emerging as critical regulators of leukocyte trafficking and inflammatory resolution. Given the paucity of studies in this area, this review summarizes current knowledge of ACKRs and CCRL2 in lung immune surveillance and discusses their potential as therapeutic targets in lung diseases.