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

Publication date: Available online 29 July 2018

Source: Journal of Autoimmunity

Author(s): Sonja M. Lacher, Christoph Thurm, Ute Distler, Alma N. Mohebiany, Nicole Israel, Maja Kitic, Anna Ebering, Yilang Tang, Matthias Klein, Guido H. Wabnitz, Florian Wanke, Yvonne Samstag, Tobias Bopp, Florian C. Kurschus, Luca Simeoni, Stefan Tenzer, Ari Waisman

Abstract

NF-κB inducing kinase (NIK) is the key protein of the non-canonical NF-κB 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^ΔT) mice. Despite showing normal development of lymphoid organs, NIK^ΔT mice were resistant to induction of CNS autoimmunity. T cells from NIK^ΔT 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 PLCγ upon TCR engagement. Hence, our data disclose a hitherto unknown function of NIK in T-cell priming and differentiation.

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