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. 2018 Nov:94:110-121.
doi: 10.1016/j.jaut.2018.07.017. Epub 2018 Jul 29.

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

Sonja M Lacher  1 , Christoph Thurm  2 , Ute Distler  3 , Alma N Mohebiany  1 , Nicole Israel  1 , Maja Kitic  1 , Anna Ebering  1 , Yilang Tang  1 , Matthias Klein  3 , Guido H Wabnitz  4 , Florian Wanke  1 , Yvonne Samstag  4 , Tobias Bopp  3 , Florian C Kurschus  1 , Luca Simeoni  2 , Stefan Tenzer  3 , Ari Waisman  5
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NF-κB inducing kinase (NIK) is an essential post-transcriptional regulator of T-cell activation affecting F-actin dynamics and TCR signaling

Sonja M Lacher et al. J Autoimmun. 2018 Nov.

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 (NIKΔT) mice. Despite showing normal development of lymphoid organs, NIKΔT mice were resistant to induction of CNS autoimmunity. T cells from NIKΔT 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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