Deletion of Nemo-like Kinase in T Cells Reduces Single-Positive CD8⁺ Thymocyte Population

The beta-catenin/Wnt signaling pathway plays an important role in all stages of T cell development. Nemo-like kinase (NLK) is an evolutionary conserved serine/threonine kinase and a negative regulator of the Wnt signaling pathway. NLK can directly phosphorylate histone deacetylase 1 (HDAC1), as well as T cell factor/lymphoid enhancer-binding factor (TCF/LEF), causing subsequent repression of target gene transcription. By engineering mice lacking NLK in early stages of T cell development, we set out to characterize the role NLK plays in T cell development and found that deletion of NLK does not affect mouse health or lymphoid tissue development. Instead, these mice harbored a reduced number of single-positive (SP) CD8(+) thymocytes without any defects in the SP CD4(+) thymocyte population. The decrease in SP CD8(+) thymocytes was not caused by a block in differentiation from double-positive CD4(+)CD8(+) cells. Neither TCR signaling nor activation was altered in the absence of NLK. Instead, we observed a significant increase in cell death and reduced phosphorylation of LEF1 as well as HDAC1 among NLK-deleted SP CD8(+) cells. Thus, NLK seems to play an important role in the survival of CD8(+) thymocytes. Our data provide evidence for a new function for NLK with regard to its involvement in T cell development and supporting survival of SP CD8(+) thymocytes.