Ly9, also known as CD229 and SLAMF3, is a homophilic receptor belonging to the signaling lymphocytic activation molecule family (SLAMF). It is predominantly expressed on B and T cells, acting as a cosignaling molecule to regulate lymphocyte homeostasis and activation, and is involved in innate and adaptive immune responses [1,3].

In Ly9 -deficient mice, iNKT cell development and lineage differentiation are affected. BALB/c.Ly9 -/- mice have expanded thymic NKT2 cells and nearly absent thymic NKT1 cells, while peripheral NKT1 cell numbers are comparable to wild-type. Also, treatment of wild-type mice with agonistic anti-Ly9 antibody impairs cytokine production and reduces spleen iNKT cell numbers [2]. Ly9 -/- mice spontaneously develop features of systemic autoimmunity, such as production of anti-nuclear antibodies, and have expanded Tfh and GC B cells. In vitro, Ly9 acts as an inhibitory receptor of IFN-γ producing CD4(+) T cells [5]. Ly9 -/- T cells show a mild Th2 defect with reduced IL-4 production and poor proliferation and low IL-2 production after suboptimal stimulation [6].

In conclusion, Ly9 plays a crucial role in lymphocyte-related immune regulation. Studies using Ly9 -/- mouse models have revealed its functions in iNKT cell development, autoimmunity, and T cell activation, providing insights into its potential as a therapeutic target for diseases like Sjögren's Syndrome, and as a biomarker for B-cell malignancies, multiple myeloma, and lung adenocarcinoma [3,4].