DC8 — Role of canonical–atypical chemokine receptor axis in resolution of inflammation

Canonical and atypical chemokine receptors work in tandem to facilitate immune cell positioning and mobilization throughout the body. While migratory signals propagate from canonical receptor activation, the roles of atypical receptors is less clear. This project seeks to resolve the specific, unresolved functions of atypical chemokine receptors (ACKRs) during the resolution of the inflammation focusing on ACKR3 and ACKR4 and their corresponding canonical counterparts CXCR4 and CCR9, respectively. The DC will refine the cooperative functions of these pairs in relevant immune cells including fibroblasts, monocytes, macrophages, and neutrophils. Next the cross-talk between ACKRs and pro-resolving mediators will be dissected through unbiased, cell analysis using RNAseq, lipidomics, and proteomics. Finally, targeting ACKR signaling by nanobodies will be evaluated for impact on immune and stromal responses. Together, these data will present mechanistic insights into how ACKRs can be exploited to promote inflammation resolution.