ArticleThe Journal of experimental medicine2012
Reduced TCR signaling potential impairs negative selection but does not result in autoimmune disease.
Article in The Journal of experimental medicine, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
34 citing papers in PubMed, 52 citations in OpenAlex.
- Parallel reactions on a single T cell receptor offer a robust kinetic proofreading mechanism.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Engineering TCR-controlled fuzzy logic into CAR T cells enhances therapeutic specificity.Cell · 2025Article
- Early events in TCR signaling - the evolving role of ITAMs.Frontiers in immunology · 2025Review
- TCR signaling induces STAT3 phosphorylation to promote TH17 cell differentiation.The Journal of experimental medicine · 2024Article
- Circulating JKAP levels may correlate with postpartum anxiety and depression through its interaction with T helper 17 cells.Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologica · 2024Article
- CD3ζ ITAMs enable ligand discrimination and antagonism by inhibiting TCR signaling in response to low-affinity peptides.Nature immunology · 2023Article
- Construction of a T cell receptor signaling range for spontaneous development of autoimmune disease.The Journal of experimental medicine · 2023Article
- Genetic Strategies to Study T Cell Development.Methods in molecular biology (Clifton, N.J.) · 2023Article
- Regulating the discriminatory response to antigen by T-cell receptor.Bioscience reports · 2022Review
- Thymic atrophy creates holes in Treg-mediated immuno-regulation via impairment of an antigen-specific clone.Immunology · 2021Article
- Attenuation of canonical NF-κB signaling maintains function and stability of human Treg.The FEBS journal · 2021Article
- Review
- The Function and Role of the Th17/Treg Cell Balance in Inflammatory Bowel Disease.Journal of immunology research · 2020Review
- The correlation between the Th17/Treg cell balance and bone health.Immunity & ageing : I & A · 2020Review
- miR-181a/b-1 controls thymic selection of Treg cells and tunes their suppressive capacity.PLoS biology · 2019Article
- TNFα-Signaling Modulates the Kinase Activity of Human Effector Treg and Regulates IL-17A Expression.Frontiers in immunology · 2019Article
- A TCR mechanotransduction signaling loop induces negative selection in the thymus.Nature immunology · 2018Article
- Interleukin-17-Producing γδ T Cells Originate from SOX13Immunity · 2018Article
- SOX4 controls invariant NKT cell differentiation by tuning TCR signaling.The Journal of experimental medicine · 2018Article
- Regulatory mechanisms in T cell receptor signalling.Nature reviews. Immunology · 2018Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Negative selection and regulatory T (T reg) cell development are two thymus-dependent processes necessary for the enforcement of self-tolerance, and both require high-affinity interactions between the T cell receptor (TCR) and self-ligands. However, it remains unclear if they are similarly impacted by alterations in TCR signaling potential. We generated a knock-in allele (6F) of the TCR ζ chain gene encoding a mutant protein lacking signaling capability whose expression is controlled by endogenous ζ regulatory sequences. Although negative selection was defective in 6F/6F mice, leading to the survival of autoreactive T cells, 6F/6F mice did not develop autoimmune disease. We found that 6F/6F mice generated increased numbers of thymus-derived T reg cells. We show that attenuation of TCR signaling potential selectively impacts downstream signaling responses and that this differential effect favors Foxp3 expression and T reg cell lineage commitment. These results identify a potential compensatory pathway for the enforcement of immune tolerance in response to defective negative selection caused by reduced TCR signaling capability.
Indexed as
Identifiers
What OpenQuestion holds
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.