TNIK signaling imprints CD8+ T cell memory formation early after priming.

Jaeger-Ruckstuhl, Carla A.; Hinterbrandner, Magdalena; Höpner, Sabine; Correnti, Colin E; Lüthi, Ursina; Friedli, Olivier; Freigang, Stefan; Al Sayed, Mohamad F; Bührer, Elias D.; Amrein, Michael A.; Schürch, Christian M.; Radpour, Ramin; Riether, Carsten; Ochsenbein, Adrian F. (2020). TNIK signaling imprints CD8+ T cell memory formation early after priming. Nature communications, 11(1), p. 1632. Nature Publishing Group 10.1038/s41467-020-15413-7

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Co-stimulatory signals, cytokines and transcription factors regulate the balance between effector and memory cell differentiation during T cell activation. Here, we analyse the role of the TRAF2-/NCK-interacting kinase (TNIK), a signaling molecule downstream of the tumor necrosis factor superfamily receptors such as CD27, in the regulation of CD8+ T cell fate during acute infection with lymphocytic choriomeningitis virus. Priming of CD8+ T cells induces a TNIK-dependent nuclear translocation of β-catenin with consecutive Wnt pathway activation. TNIK-deficiency during T cell activation results in enhanced differentiation towards effector cells, glycolysis and apoptosis. TNIK signaling enriches for memory precursors by favouring symmetric over asymmetric cell division. This enlarges the pool of memory CD8+ T cells and increases their capacity to expand after re-infection in serial re-transplantation experiments. These findings reveal that TNIK is an important regulator of effector and memory T cell differentiation and induces a population of stem cell-like memory T cells.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Service Sector > Institute of Pathology
04 Faculty of Medicine > Service Sector > Institute of Pathology > Immunopathology
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR)
04 Faculty of Medicine > Service Sector > Institute of Pathology > Clinical Pathology
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Tumor-Immunologie
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Tumor-Immunologie

04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Clinic of Medical Oncology

Graduate School:

Graduate School for Cellular and Biomedical Sciences (GCB)

UniBE Contributor:

Ruckstuhl, Carla Alicia; Hinterbrandner, Magdalena; Höpner, Sabine; Lüthi, Ursina; Friedli, Olivier; Freigang, Stefan Bernd; Bührer, Elias; Amrein, Michael Alex; Schürch, Christian; Radpour, Ramin; Riether, Carsten and Ochsenbein, Adrian

Subjects:

500 Science > 570 Life sciences; biology
600 Technology > 610 Medicine & health

ISSN:

2041-1723

Publisher:

Nature Publishing Group

Funders:

[4] Swiss National Science Foundation

Language:

English

Submitter:

Rebeka Gerber

Date Deposited:

12 Aug 2020 16:56

Last Modified:

20 Jan 2021 14:51

Publisher DOI:

10.1038/s41467-020-15413-7

PubMed ID:

32242021

BORIS DOI:

10.7892/boris.145786

URI:

https://boris.unibe.ch/id/eprint/145786

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