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

6533b852fe1ef96bd12aacaa

RESEARCH PRODUCT

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

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

subject

Central Nervous System 0301 basic medicine Encephalomyelitis Autoimmune Experimental T-Lymphocytes T cell Primary Cell Culture Immunology Receptors Antigen T-Cell Priming (immunology)Protein Serine-Threonine Kinases Biology Lymphocyte Activation Immunological synapse Mice 03 medical and health sciences 0302 clinical medicine Immune system medicine Animals Immunology and Allergy Protein kinase B Adaptor Proteins Signal Transducing Mice Knockout Mitogen-Activated Protein Kinase 1 Mitogen-Activated Protein Kinase 3 ZAP-70 Protein-Tyrosine Kinase Phospholipase C gamma Gene Expression Profiling ZAP70 T-cell receptor Membrane Proteins Phosphoproteins Actins Peptide Fragments Cell biology Mice Inbred C57BL 030104 developmental biology medicine.anatomical_structure Gene Expression Regulation 030220 oncology & carcinogenesis Myelin-Oligodendrocyte Glycoprotein Lymph Nodes Signal transduction T-Box Domain Proteins Proto-Oncogene Proteins c-akt Spleen Signal Transduction

description

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.

year	journal	country	edition	language
2018-11-01	Journal of Autoimmunity

https://doi.org/10.1016/j.jaut.2018.07.017