ArticleNature immunology2012
Constitutive MHC class I molecules negatively regulate TLR-triggered inflammatory responses via the Fps-SHP-2 pathway.
Article in Nature immunology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 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.
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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
66 citing papers in PubMed, 126 citations in OpenAlex.
- The Cytoplasmic Domain of MHC Class I Molecules as a Molecular Switch: A Perspective from Short Linear Motifs and Intrinsically Disordered Regions.Biomolecules · 2026Review
- CXCL16-driven CD4Journal for immunotherapy of cancer · 2026Article
- Isoalantolactone induces AML pyroptosis and potentiatesActa pharmaceutica Sinica. B · 2026Article
- Regulation and activity of the phosphatase SHP2: SH2 domains, dephosphorylation activity, and beyond.Biochemical Society transactions · 2026Review
- Toll-like receptors in innate immunity and inflammation: from fundamental biology to clinic insights.Immunity & inflammation · 2026Review
- Granulocyte-macrophage colony-stimulating factor may contribute to spondyloarthritis development in HLA-B27 transgenic rat by affecting conventional dendritic cells function.Arthritis research & therapy · 2025Article
- Mutation of conserved MHC class I cytoplasmic tyrosine affects CD8+ T cell priming, effector function, and memory response.Frontiers in immunology · 2025Article
- Immunogenicity of lipid nanoparticles and its impact on the efficacy of mRNA vaccines and therapeutics.Experimental & molecular medicine · 2023Review
- Outside-in signaling through the major histocompatibility complex class-I cytoplasmic tail modulates glutamate receptor expression in neurons.Scientific reports · 2023Article
- Soluble CD4 effectively prevents excessive TLR activation of resident macrophages in the onset of sepsis.Signal transduction and targeted therapy · 2023Article
- SLAMF7 regulates the inflammatory response in macrophages during polymicrobial sepsis.The Journal of clinical investigation · 2023Article
- Setting sail: Maneuvering SHP2 activity and its effects in cancer.Advances in cancer research · 2023Review
- Establishing the role of the FES tyrosine kinase in the pathogenesis, pathophysiology, and severity of sepsis and its outcomes.Frontiers in immunology · 2023Article
- A comprehensive review of SHP2 and its role in cancer.Cellular oncology (Dordrecht, Netherlands) · 2022Review
- SRRM2 organizes splicing condensates to regulate alternative splicing.Nucleic acids research · 2022Article
- Effects of a multicomponent microbial feed additive containing prebiotics and probiotics on health, immune status, metabolism, and performance of newly weaned beef steers during a 35-d receiving period.Translational animal science · 2022Article
- Article
- Inducible downregulation of miR-93 feedback promotes innate responses against RNA virus by amplifying interferon signaling.American journal of translational research · 2022Article
- Microglia and macrophage exhibit attenuated inflammatory response and ferroptosis resistance after RSL3 stimulation via increasing Nrf2 expression.Journal of neuroinflammation · 2021Article
- Open MHC Class I Conformers: A Look through the Looking Glass.International journal of molecular sciences · 2021Review
6 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The molecular mechanisms that fine-tune Toll-like receptor (TLR)-triggered innate inflammatory responses remain to be fully elucidated. Major histocompatibility complex (MHC) molecules can mediate reverse signaling and have nonclassical functions. Here we found that constitutively expressed membrane MHC class I molecules attenuated TLR-triggered innate inflammatory responses via reverse signaling, which protected mice from sepsis. The intracellular domain of MHC class I molecules was phosphorylated by the kinase Src after TLR activation, then the tyrosine kinase Fps was recruited via its Src homology 2 domain to phosphorylated MHC class I molecules. This led to enhanced Fps activity and recruitment of the phosphatase SHP-2, which interfered with TLR signaling mediated by the signaling molecule TRAF6. Thus, constitutive MHC class I molecules engage in crosstalk with TLR signaling via the Fps-SHP-2 pathway and control TLR-triggered innate inflammatory responses.
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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 Socratic graph.