Our research also focuses on the regulation of a potassium channel, KCa3.1 (also known as SK4, IKCa, and KCNN4), and its role in the activation of T and B lymphocytes. KCa3.1 is required for calcium influx in a subset of T and B lymphocytes, which is critical for the subsequent activation these cells. Due to the importance of KCa3.1 in the activation of immune cells, inhibitors of KCa3.1 are in development to treat autoimmune diseases such as systemic lupus erythematosus and asthma, and to prevent rejection of transplanted organs, underscoring the importance in understanding how these channels are regulated.
We recently identified several new molecules in T and B cells that either positively or negatively regulate KCa3.1 channel activity and, via their effects on KCa3.1, either postively or negatively regulate activation of these cells. One example of signaling protein that we have identified that is required in KCa3.1 channel activity is nucleoside diphosphate kinase B (NDPK-B).
We found that NDPK directly phosphorylates and activates KCa3.1 channel activity and is required for the subsequent activation T and B lymphocytes. Moreover, we have generated NDPK knockout mice and have found that T and B cell activation is impaired in these mice. These and other knockout mice we have generated are being studied to address whether loss of KCa3.1 and NDPK-B is protective against autoimmune disease and/or the ability to reject an allogeneic transplant, which would justify the development of inhibitors of these molecules to treat disease in humans.