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. ACKRs like Ackr1 control chemokine gradients independently of G-proteins and have functions related to chemokine immobilization, cellular movement, and recruitment of 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, thereby inhibiting TAAD progression. Conversely, overexpression of Ackr1 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+ macrophages migration, and in human liver cirrhosis, ACKR1+ endothelial cells enhance leucocyte transmigration [3,4].

In conclusion, Ackr1 plays a crucial role in regulating chemokine-related functions, especially in inflammation-associated diseases. Gene-knockout or knockdown models have revealed its significance in diseases like TAAD and tendon adhesion, highlighting its potential as a therapeutic target for these conditions.