ArticleJCI insight2021
Anti-TIGIT differentially affects sepsis survival in immunologically experienced versus previously naive hosts.
Article in JCI insight, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 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
12 citing papers in PubMed, 17 citations in OpenAlex.
- Lymphocyte function inhibition and exhaustion in sepsis: mechanisms and applications.Frontiers in immunology · 2026Review
- Sepsis-associated immunosuppression: mechanistic Insights, Biomarkers, and therapeutic perspectives.Molecular biology reports · 2025Review
- The Multifaceted Role of Regulatory T Cells in Sepsis: Mechanisms, Heterogeneity, and Pathogen-Tailored Therapies.International journal of molecular sciences · 2025Review
- Tim-3 pathway dysregulation and targeting in sepsis-induced immunosuppression.European journal of medical research · 2024Review
- TIGIT stimulation suppresses autoimmune uveitis by inhibiting Th17 cell infiltration.Journal of leukocyte biology · 2024Article
- TIGIT regulates CD4Frontiers in immunology · 2024Article
- The Calm after the Storm: Implications of Sepsis Immunoparalysis on Host Immunity.Journal of immunology (Baltimore, Md. : 1950) · 2023Review
- Sepsis-induced changes in differentiation, maintenance, and function of memory CD8 T cell subsets.Frontiers in immunology · 2023Review
- Inflammation Controls Susceptibility of Immune-Experienced Mice to Sepsis.ImmunoHorizons · 2022Article
- Regulatory T Cells: Angels or Demons in the Pathophysiology of Sepsis?Frontiers in immunology · 2022Review
- TIGIT Deficiency Protects Mice From DSS-Induced Colitis by Regulating IL-17A-Producing CD4Frontiers in immunology · 2022Article
- Severity of Sepsis Determines the Degree of Impairment Observed in Circulatory and Tissue-Resident Memory CD8 T Cell Populations.Journal of immunology (Baltimore, Md. : 1950) · 2021Article
Corrections and comments
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Authors and funding
9 authors at 1 institution in 2 countries.
Funding
Abstract
Mounting evidence suggests that the balance of T cell costimulatory and coinhibitory signals contributes to mortality during sepsis. Here, we identified a critical role of the coinhibitory molecule T cell Ig and ITIM domain (TIGIT) in regulating sepsis mortality. Because TIGIT is significantly upregulated on memory T cells, we developed a "memory mouse" model to study the role of TIGIT during sepsis in a more physiologically relevant context. Mice received sequential pathogen exposure and developed memory T cell frequencies, similar to those observed in adult humans, and were then subjected to sepsis induction via cecal ligation and puncture. Our results show that targeting the TIGIT pathway during sepsis is fundamentally different in previously naive versus memory mice, in that αTIGIT Ab had no effect on survival in previously naive septic mice but sharply worsened survival in memory septic mice. Mechanistically, αTIGIT increased apoptosis of memory T cells, decreased T cell function, and downregulated the costimulatory receptor DNAM on memory CD8+ T cells in memory septic mice, but not in previously naive septic mice. Additionally, αTIGIT diminished Helios expression in Tregs in memory but not previously naive septic mice. These data highlight fundamental differences in the pathophysiological impact of targeting TIGIT in immunologically experienced versus previously naive hosts during sepsis.
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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.