LY6E, also known as lymphocyte antigen 6 complex, locus E, is a canonical lymphocyte antigen-6/urokinase-type plasminogen activator receptor Ly6/uPAR family protein. It plays crucial roles in immunological regulation, T cell physiology, and oncogenesis. Emerging evidence shows its involvement in modulating viral infection, especially in restricting the entry of certain viruses [2].

Using conditional Ly6e knockout (KO) mouse models, several studies have revealed its significance in antiviral defense. Mice with Ly6e loss in Lyz2-expressing cells, radioresistant Vav1-expressing cells, and non-haematopoietic cells were more susceptible to murine coronavirus. Global conditional loss of Ly6e led to clinical disease and higher viral burden after SARS-CoV-2 infection [1,3]. These models demonstrated that Ly6e expression in secretory club and ciliated cells protected them from SARS-CoV-2 infection and preserved an epithelial cell transcriptomic signature in the lung [1].

In conclusion, Ly6e is a key antiviral immune effector, especially effective against coronaviruses. Conditional Ly6e KO mouse models have been instrumental in understanding its role in protecting against respiratory coronavirus infections, highlighting its potential as a target for developing strategies against such viral diseases.