Cx3cr1, the gene encoding the fractalkine receptor, functions as the specific receptor for the chemokine CX3CL1 [4]. Signaling within the CX3CL1-Cx3cr1 axis plays a crucial role in many processes related to inflammation, the immune response, and cell-cell communication within the immune system [1,4,6]. Engagement with CX3CL1 initiates downstream signaling pathways regulating various biological functions [4].

In a murine peritoneal dialysis (PD) model, Cx3cr1, mostly expressed on macrophages in the peritoneal wall, promoted fibrosis induced by chronic dialysate exposure. This was due to a positive feedback loop where interaction with Cx3CR1-expressing macrophages promoted mesothelial expression of CX3CL1 and TGFβ expression, and TGFβ in turn upregulated Cx3cr1 in murine and human monocytic cells [2].

In a germinal matrix hemorrhage (GMH) rat model, administration of CX3CR1 CRISPR or a CX3CR1 inhibitor (AZD8797) abolished the protective effect of recombinant fractalkine (r-FKN). r-FKN activated CX3CR1 to promote hematoma resolution, attenuate neuroinflammation, and improve neurological deficits partially through the AMPK/PPARγ signaling pathway [3].

In familial tauopathy, a marked reduction in the expression of Cx3cr1 was observed in monocytes and NK cells from carriers of pathogenic variants in MAPT compared to healthy non-carrier controls [5].

In conclusion, Cx3cr1 is essential in processes like inflammation, immune response, and cell-cell communication. Through gene-knockout or related models, its role in diseases such as peritoneal fibrosis, GMH-related neurological deficits, and potentially tau-associated neurodegenerative diseases has been revealed. These findings contribute to understanding the mechanisms of these diseases and may provide new therapeutic targets.