ArticlePloS one2017
CXCR4 blockade decreases CD4+ T cell exhaustion and improves survival in a murine model of polymicrobial sepsis.
Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 41 citations in OpenAlex.
- Histone marks identify novel transcription factors that parse CAR-T subset-of-origin, clinical potential and expansion.Nature communications · 2024Trial
- A Phase Ib/II Trial of the First-in-Class Anti-CXCR4 Antibody Ulocuplumab in Combination with Lenalidomide or Bortezomib Plus Dexamethasone in Relapsed Multiple Myeloma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2020Trial
- Machine learning-driven decoding of maternal immune signatures in repeated pregnancy loss.PLoS computational biology · 2026Article
- Lymphocyte function inhibition and exhaustion in sepsis: mechanisms and applications.Frontiers in immunology · 2026Review
- Multi-omic analysis of PBMCs in sepsis reveals widespread cytotoxic dysfunction and an increased population ofFrontiers in immunology · 2025Article
- Chemokines Signature and T Cell Dynamics in Leishmaniasis: Molecular insight and therapeutic application.Expert reviews in molecular medicine · 2024Review
- Plerixafor for pathogen-agnostic treatment in murine thigh infection and zebrafish sepsis.Clinical and translational science · 2024Article
- A narrative review of chemokine receptors CXCR1 and CXCR2 and their role in acute respiratory distress syndrome.European respiratory review : an official journal of the European Respiratory Society · 2024Review
- Advancements in microenvironment-based therapies: transforming the landscape of multiple myeloma treatment.Frontiers in oncology · 2024Review
- Cancer and sepsis.Clinical science (London, England : 1979) · 2023Article
- Pathophysiology of Sepsis and Genesis of Septic Shock: The Critical Role of Mesenchymal Stem Cells (MSCs).International journal of molecular sciences · 2022Review
- Article
- Expression of PD-1 on Memory T Lymphocytes Predicts 28-Day Mortality of Patients with Sepsis: A Prospective Observational Study.Journal of inflammation research · 2022Article
- TLR2-induced CD8Frontiers in immunology · 2022Article
- Altered expressions of CXCR4 and CD26 on T-helper lymphocytes in hereditary hemorrhagic telangiectasia.Orphanet journal of rare diseases · 2021Article
- TIGIT modulates sepsis-induced immune dysregulation in mice with preexisting malignancy.JCI insight · 2021Article
- The IL-27 receptor regulates TIGIT on memory CD4iScience · 2021Article
- Atezolizumab alleviates the immunosuppression induced by PD‑L1‑positive neutrophils and improves the survival of mice during sepsis.Molecular medicine reports · 2021Article
- Preexisting malignancy abrogates the beneficial effects of CXCR4 blockade during sepsis.Journal of leukocyte biology · 2020Article
- Three Genes Predict Prognosis in Microenvironment of Ovarian Cancer.Frontiers in genetics · 2020Article
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
Sepsis is a dysregulated systemic response to infection involving many inflammatory pathways and the induction of counter-regulatory anti-inflammatory processes that results in a state of immune incompetence and can lead to multi-organ failure. CXCR4 is a chemokine receptor that, following ligation by CXCL12, directs cells to bone marrow niches and also plays an important role in T cell cosignaling and formation of the immunological synapse. Here, we investigated the expression and function of CXCR4 in a murine model of polymicrobial sepsis. Results indicate that CXCR4 is selectively upregulated on naïve CD4+ and CD8+ T cells and CD4+ central memory T cells following the induction of sepsis, and that CXCR4 antagonism resulted in a significant decrease in sepsis-induced mortality. We probed the mechanistic basis for these findings and found that CXCR4 antagonism significantly increased the number of peripheral CD4+ and CD8+ T cells following sepsis. Moreover, mice treated with the CXCR4 antagonist contained fewer PD-1+ LAG-3+ 2B4+ cells, suggesting that blockade of CXCR4 mitigates CD4+ T cell exhaustion during sepsis. Taken together, these results characterize CXCR4 as an important pathway that modulates immune dysfunction and mortality following sepsis, which may hold promise as a target for future therapeutic intervention in septic patients.
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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.