ArticleNature2011
Dampening of death pathways by schnurri-2 is essential for T-cell development.
Article in Nature, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
30 citing papers in PubMed, 36 citations in OpenAlex.
- Mechanisms of T cell activation: Integrating signaling pathways, experimental models, and therapeutic implications.EXCLI journal · 2026Review
- Prior chemotherapy deteriorates T-cell quality for CAR T-cell therapy in B-cell non-Hodgkin's lymphoma.Journal for immunotherapy of cancer · 2025Article
- Aberrant CD8Frontiers in immunology · 2024Article
- Vertebrate-conserved Schnurri zinc fingers restrain Drosophila vein patterning.microPublication biology · 2024Article
- A Beginner's Guide to T Cell Development.Methods in molecular biology (Clifton, N.J.) · 2023Review
- Schnurri 3 promotes Th2 cytokine production during the late phase of T-cell antigen stimulation.European journal of immunology · 2022Article
- Functional CRISPR dissection of gene networks controlling human regulatory T cell identity.Nature immunology · 2020Article
- Article
- HIV-1 infection increases microRNAs that inhibit Dicer1, HRB and HIV-EP2, thereby reducing viral replication.PloS one · 2019Article
- The ESCRT protein CHMP5 escorts αβ T cells through positive selection.Cellular & molecular immunology · 2018Article
- Post-translational control of T cell development by the ESCRT protein CHMP5.Nature immunology · 2017Article
- Article
- Expression of Twist2 is controlled by T-cell receptor signaling and determines the survival and death of thymocytes.Cell death and differentiation · 2016Article
- Homocysteine activates T cells by enhancing endoplasmic reticulum-mitochondria coupling and increasing mitochondrial respiration.Protein & cell · 2016Article
- Loss-of-function variants in HIVEP2 are a cause of intellectual disability.European journal of human genetics : EJHG · 2016Article
- CBAP promotes thymocyte negative selection by facilitating T-cell receptor proximal signaling.Cell death & disease · 2014Article
- N-glycosylation bidirectionally extends the boundaries of thymocyte positive selection by decoupling Lck from Ca²⁺ signaling.Nature immunology · 2014Article
- The Dpp/TGFβ-dependent corepressor Schnurri protects epithelial cells from JNK-induced apoptosis in drosophila embryos.Developmental cell · 2014Article
- The self-obsession of T cells: how TCR signaling thresholds affect fate 'decisions' and effector function.Nature immunology · 2014Review
- Organelle-specific initiation of cell death.Nature cell biology · 2014Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Generation of a diverse and self-tolerant T-cell repertoire requires appropriate interpretation of T-cell antigen receptor (TCR) signals by CD4(+ ) CD8(+) double-positive thymocytes. Thymocyte cell fate is dictated by the nature of TCR-major-histocompatibility-complex (MHC)-peptide interactions, with signals of higher strength leading to death (negative selection) and signals of intermediate strength leading to differentiation (positive selection). Molecules that regulate T-cell development by modulating TCR signal strength have been described but components that specifically define the boundaries between positive and negative selection remain unknown. Here we show in mice that repression of TCR-induced death pathways is critical for proper interpretation of positive selecting signals in vivo, and identify schnurri-2 (Shn2; also known as Hivep2) as a crucial death dampener. Our results indicate that Shn2(-/-) double-positive thymocytes inappropriately undergo negative selection in response to positive selecting signals, thus leading to disrupted T-cell development. Shn2(-/-) double-positive thymocytes are more sensitive to TCR-induced death in vitro and die in response to positive selection interactions in vivo. However, Shn2-deficient thymocytes can be positively selected when TCR-induced death is genetically ablated. Shn2 levels increase after TCR stimulation, indicating that integration of multiple TCR-MHC-peptide interactions may fine-tune the death threshold. Mechanistically, Shn2 functions downstream of TCR proximal signalling compenents to dampen Bax activation and the mitochondrial death pathway. Our findings uncover a critical regulator of T-cell development that controls the balance between death and differentiation.
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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.