Targeting natural killer cell reactivity by employing antibody to NKp46: implications for type 1 diabetes (THER6P.857) Academic Article uri icon

abstract

  • Natural killer (NK) cells belong to the innate lymphoid cells. NK cells are able to eliminate transformed cells and virus-infected cells without the need of prior antigen stimulation. Their cytotoxic activity is regulated through the delicate balance between activating and inhibitory signals. NKp46 is a member of the primary activating receptors of NK cells; and it is reported to interact with the hemagglutinin (HA) of the influenza virus, heparan sulfate and vimentin. Moreover, our group and others have reported that NKp46 is involved in the development of type 1 diabetes (T1D) autoimmune disease. Subsequently, we hypothesized that blocking of the NKp46 could prevent T1D development or prolong its honeymoon period. To address this goal we characterized monoclonal antibodies for the murine NKp46. One mAb, F15, was able to down-regulate the surface expression of NKp46 on primary murine NK cell following antibody injection. Additionally, F15 treatments were able to down-regulate cytotoxic activity mediated by NKp46, but not by other NK receptors. To test our primary assumption, we examined T1D development in two models, NOD mice and low-dose streptozotocin. The results showed significantly lower incidence of diabetic mice in the F15-treated group comparing to control groups. This study directly demonstrates the involvement of NKp46 in T1D development and suggests possible treatment for early insulitis

publication date

  • January 1, 2014