NF-κB inducing kinase (NIK) is an essential post-transcriptional regulator of T-cell activation affecting F-actin dynamics and TCR signaling

NF-kappa B inducing kinase (NIK) is the key protein of the non-canonical NF-kappa B pathway and is important for the development of lymph nodes and other secondary immune organs. We elucidated the specific role of NIK in T cells using T-cell specific NIK-deficient (NIK Delta T) mice. Despite showing normal development of lymphoid organs, NIK Delta T mice were resistant to induction of CNS autoimmunity. T cells from MCAT mice were deficient in late priming, failed to up-regulate T-bet and to transmigrate into the CNS. Proteomic analysis of activated NIK-/.T cells showed de-regulated expression of proteins involved in the formation of the immunological synapse: in particular, proteins involved in cytoskeleton dynamics. In line with this we found that NIK-deficient T cells were hampered in phosphorylation of Zap70, LAT, AKT, ERK1/2 and PLC gamma upon TCR engagement. Hence, our data disclose a hitherto unknown function of NIK in T-cell priming and differentiation.