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 multiple tissue-resident immune cell subsets and is thus considered a marker of tissue retention. It regulates T-cell subset functions, determining migration-retention ratios and the acquisition of effector or regulatory phenotypes. It is involved in pathways related to Treg cell differentiation and cytokine secretion such as IFN-γ, IL-17, and IL-22 [1].

In Cd69 -/- mice, after myocardial infarction, there was a strong IL-17+ γδT cell response, increasing myocardial inflammation and worsening cardiac function, while CD69+ Tregs induced apoptosis and decreased IL-17A production in γδT cells [2]. In colitis mouse models, iTregs from CD4 Cre CD69 fl/fl mice failed to alleviate colitis, indicating that Cd69 is crucial for the immunosuppressive function of Tregs [3].

In conclusion, Cd69 is a key regulator in the immune system, influencing T-cell activation, differentiation, and retention. Gene knockout mouse models have revealed its importance in diseases like myocardial infarction and colitis, providing insights into its role in immune-related pathological processes and suggesting its potential as a therapeutic target.

References:

1. Cibrián, Danay, Sánchez-Madrid, Francisco. . CD69: from activation marker to metabolic gatekeeper. In European journal of immunology, 47, 946-953. doi:10.1002/eji.201646837. https://pubmed.ncbi.nlm.nih.gov/28475283/

2. Blanco-Domínguez, Rafael, de la Fuente, Hortensia, Rodríguez, Cristina, Martínez-González, José, Martín, Pilar. 2022. CD69 expression on regulatory T cells protects from immune damage after myocardial infarction. In The Journal of clinical investigation, 132, . doi:10.1172/JCI152418. https://pubmed.ncbi.nlm.nih.gov/36066993/

3. Yu, Lei, Zhou, Bingluo, Zhu, Yiran, Wang, Jianli, Jin, Hongchuan. 2023. HSF1 promotes CD69+ Treg differentiation to inhibit colitis progression. In Theranostics, 13, 1892-1905. doi:10.7150/thno.78078. https://pubmed.ncbi.nlm.nih.gov/37064870/