Clec4a4, also known as DCIR2 (Dendritic cell immunoreceptor 2), is a C-type lectin receptor. It is mainly expressed by CD8α-DCs and can modulate T cell immunity, playing a role in regulating the function of dendritic cells (DCs) and affecting immune responses [1,3].

In atherosclerosis, Clec4a4 deficiency in Ldlr -/- mice leads to reduced atherosclerotic plaque formation, along with altered lipid metabolism and myeloid immune cell distribution, suggesting a pro-atherosclerotic role of Clec4a4 [1].

In tumor immunity, mClec4A4 (murine Clec4A4) deficiency reduces tumor development due to enhanced antitumor immune responses and an improved immunosuppressive tumor microenvironment, indicating it acts as a negative immune checkpoint regulator [2].

In addition, Clec4a4 -/- CD8α-cDCs show enhanced cytokine production and T-cell priming, and Clec4a4 -/- mice exhibit TLR-mediated hyperinflammation, augmented T-cell responses, and progressive autoimmune pathogenesis upon antigenic immunization, highlighting its role in regulating the magnitude and quality of immune response [3].

In conclusion, Clec4a4 is a key regulator in immune-related processes. Its deficiency in KO mouse models reveals its pro-atherosclerotic role and its function as a negative immune checkpoint regulator in tumor immunity. These findings contribute to understanding the mechanisms of atherosclerosis and tumor development, potentially providing new targets for related disease treatments.