Ackr1, previously known as the Duffy antigen receptor for chemokines (DARC), is a key regulator in the chemokine network. It binds chemokines involved in inflammatory responses, cancer proliferation, angiogenesis, and metastasis. Ackr1 controls chemokine gradients independently of G-proteins and has functions related to chemokine immobilization, cellular movement, and recruitment of effectors like β-arrestins [2].

In type A aortic dissection (TAAD), knockdown of Ackr1 in endothelial cells suppressed the NF-κB signaling pathway and SPP1 expression, reducing macrophage migration and polarization, thus inhibiting TAAD progression. Conversely, overexpression exacerbated TAAD. Amikacin, an Ackr1-targeted drug, regulated macrophage behavior via the Ackr1/NF-κB/SPP1 pathway, attenuating TAAD progression in mice [1]. In tendon adhesion, Ackr1 was verified to regulate FOLR2+ macrophage migration. Transplantation experiments using Ackr1 -/- chimeras showed that compared with wild-type chimeras, the decline of FOLR2+ macrophages was observed, indicating Ackr1's specific involvement in FOLR2+ macrophage migration [3].

In conclusion, Ackr1 plays a crucial role in regulating macrophage-related processes in diseases such as TAAD and tendon adhesion. Studies using gene knockout (KO) mouse models, like the Ackr1 -/- chimeras, have been instrumental in revealing its role in these disease conditions, providing potential therapeutic targets for these diseases.

References:

1. Wang, Yayu, Jia, Xiong, Zhang, Yifei, Zou, Chang, Zheng, Qijun. 2024. ACKR1hiECs Promote Aortic Dissection Through Adjusting Macrophage Behavior. In Circulation research, 136, 211-228. doi:10.1161/CIRCRESAHA.124.325458. https://pubmed.ncbi.nlm.nih.gov/39692014/

2. Crawford, Kyler S, Volkman, Brian F. 2023. Prospects for targeting ACKR1 in cancer and other diseases. In Frontiers in immunology, 14, 1111960. doi:10.3389/fimmu.2023.1111960. https://pubmed.ncbi.nlm.nih.gov/37006247/

3. Zhang, Xinshu, Xiao, Yao, Hu, Bo, Li, Baojie, Liu, Shen. 2024. Multi-omics analysis of human tendon adhesion reveals that ACKR1-regulated macrophage migration is involved in regeneration. In Bone research, 12, 27. doi:10.1038/s41413-024-00324-w. https://pubmed.ncbi.nlm.nih.gov/38714649/