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 and acts as a cosignaling molecule, regulating lymphocyte homeostasis and activation. It is involved in innate and adaptive immune responses, and its genomic region is associated with the predisposition to systemic lupus erythematosus (SLE) [1,3,4].

Ly9 -/- mice on a BALB/c background showed an expanded population of thymic NKT2 cells and nearly absent NKT1 cells in the thymus, while peripheral NKT1 cell numbers were comparable to wild-type mice, indicating its role in iNKT cell lineage differentiation [2]. Ly9 -/- mice spontaneously developed features of systemic autoimmunity, such as autoantibody production, with expanded Tfh and GC B cells in aged mice, and Ly9 acts as an inhibitory receptor of IFN-γ producing CD4(+) T cells [4]. Also, Ly9 -/- T cells had a mild Th2 defect and poor proliferation and IL-2 production after suboptimal stimulation [5].

In conclusion, Ly9 is crucial for lymphocyte homeostasis and activation, playing a significant role in iNKT cell development, prevention of autoimmunity, and T cell activation. Studies using Ly9 knockout mouse models have provided valuable insights into its functions in these immune-related processes and disease-associated conditions [2,4,5].