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

Autor: Lacher SM; Institute for Molecular Medicine, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany., Thurm C; Institute of Molecular and Clinical Immunology, Health Campus Immunology, Infectiology, and Inflammation, Otto von Guericke University, Magdeburg, Germany., Distler U; Institute for Immunology, University Medical Center of the Johannes-Gutenberg University Mainz, Mainz, Germany., Mohebiany AN; Institute for Molecular Medicine, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany., Israel N; Institute for Molecular Medicine, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany., Kitic M; Institute for Molecular Medicine, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany., Ebering A; Institute for Molecular Medicine, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany., Tang Y; Institute for Molecular Medicine, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany., Klein M; Institute for Immunology, University Medical Center of the Johannes-Gutenberg University Mainz, Mainz, Germany., Wabnitz GH; Institute of Immunology, Section Molecular Immunology, Ruprecht-Karls-University, Heidelberg, Germany., Wanke F; Institute for Molecular Medicine, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany., Samstag Y; Institute of Immunology, Section Molecular Immunology, Ruprecht-Karls-University, Heidelberg, Germany., Bopp T; Institute for Immunology, University Medical Center of the Johannes-Gutenberg University Mainz, Mainz, Germany., Kurschus FC; Institute for Molecular Medicine, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany., Simeoni L; Institute of Molecular and Clinical Immunology, Health Campus Immunology, Infectiology, and Inflammation, Otto von Guericke University, Magdeburg, Germany., Tenzer S; Institute for Immunology, University Medical Center of the Johannes-Gutenberg University Mainz, Mainz, Germany., Waisman A; Institute for Molecular Medicine, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany. Electronic address: Waisman@uni-mainz.de.
Jazyk: angličtina
Zdroj: Journal of autoimmunity [J Autoimmun] 2018 Nov; Vol. 94, pp. 110-121. Date of Electronic Publication: 2018 Jul 29.
DOI: 10.1016/j.jaut.2018.07.017
Abstrakt: 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.
(Copyright © 2018. Published by Elsevier Ltd.)
Databáze: MEDLINE
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