ArticleNature communications2023
Themis2 regulates natural killer cell memory function and formation.
Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
What it found
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Who cites it
8 citing papers in PubMed, 12 citations in OpenAlex.
- Genome-wide profiling of salivary promoter-region DNA methylation in periodontitis: the Tromsø Study.BMC medical genomics · 2026Article
- Gene regulatory network transitions reveal the central transcription factors in lung adenocarcinoma progression.NPJ systems biology and applications · 2026Article
- Mapping NK cell diversity in response to COVID-19 and mRNA vaccination.Scientific reports · 2025Article
- Immunocyte phenotypes and childhood disease susceptibility: insights from bidirectional Mendelian randomization and implications for immunomodulatory therapies.Naunyn-Schmiedeberg's archives of pharmacology · 2025Article
- THEMIS2 contributes to ovarian cancer metastasis via DOCK4-mediated activation of Rap1 signaling.Cellular oncology (Dordrecht, Netherlands) · 2025Article
- Natural killer cell memory: challenges and opportunities for cancer immunotherapy.Cancer biology & therapy · 2024Review
- No time to die: Epigenetic regulation of natural killer cell survival.Immunological reviews · 2024Review
- Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Immunological memory is a hallmark of the adaptive immune system. Although natural killer (NK) cells are innate immune cells important for the immediate host defence, they can differentiate into memory NK cells. The molecular mechanisms controlling this differentiation are yet to be fully elucidated. Here we identify the scaffold protein Themis2 as a critical regulator of memory NK cell differentiation and function. Themis2-deficient NK cells expressing Ly49H, an activating NK receptor for the mouse cytomegalovirus (MCMV) antigen m157, show enhanced differentiation into memory NK cells and augment host protection against MCMV infection. Themis2 inhibits the effector function of NK cells after stimulation of Ly49H and multiple activating NK receptors, though not specific to memory NK cells. Mechanistically, Themis2 suppresses Ly49H signalling by attenuating ZAP70/Syk phosphorylation, and it also translocates to the nucleus, where it promotes Zfp740-mediated repression to regulate the persistence of memory NK cells. Zfp740 deficiency increases the number of memory NK cells and enhances the effector function of memory NK cells, which further supports the relevance of the Themis2-Zfp740 pathway. In conclusion, our study shows that Themis2 quantitatively and qualitatively regulates NK cell memory formation.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.