Cd69, also known as activation inducer molecule, very early activation antigen, MLR-3 and Leu-23, is a membrane-bound, type II C-lectin receptor. It is a classical early marker of lymphocyte activation, rapidly appearing on the plasma membrane surface after stimulation. Cd69 is expressed by several tissue-resident immune cell subsets. It is involved in regulating the migration-retention ratio of T-cell subsets, determining their effector or regulatory phenotypes. It also plays a role in Treg cell differentiation and the secretion of cytokines like IFN-γ, IL-17, and IL-22. Additionally, it is related to the metabolic reprogramming regulating TH-effector lineages [1].

In Cd69-/-mice, after myocardial infarction, there was a strong IL-17+ γδT cell response, increasing myocardial inflammation and worsening cardiac function. This indicates that Cd69 expression on Tregs is crucial for protecting from immune damage after myocardial infarction [2]. In colitis mouse models, iTregs from CD4 Cre CD69 fl/fl mice failed to alleviate colitis, and genetic or chemical inhibition of HSF1, which promotes CD69+ Treg differentiation, impaired this process and promoted colitis pathogenesis. Conversely, stabilizing HSF1 enhanced CD69+ Treg differentiation and alleviated colitis [3].

In conclusion, Cd69 is essential in regulating T-cell functions, including activation, differentiation, and retention. Through gene knockout mouse models, its significance in diseases such as myocardial infarction and colitis has been revealed. These models have provided insights into how Cd69-mediated immunoregulation impacts disease development, suggesting its potential as a therapeutic target in these disease areas.