ArticlePloS one2015
CCR4 Controls the Suppressive Effects of Regulatory T Cells on Early and Late Events during Severe Sepsis.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 33 citations in OpenAlex.
- T-cell dysfunction and death in sepsis: a mechanistic review.Frontiers in immunology · 2026Review
- Computational and Experimental Biology Reveals Dihydroartemisinin's Efficacy Against Steroid-Induced Osteonecrosis of the Femoral Head Adjusting Ferroptosis via CCL17-PRDX6.Drug design, development and therapy · 2026Article
- Interleukin-27-producing cells in gram-negative neonatal sepsis display diverse phenotypes and functions in the liver.ImmunoHorizons · 2025Article
- The Impact of Steatotic Liver Disease on Cytokine and Chemokine Kinetics During Sepsis.International journal of molecular sciences · 2025Article
- CTLA-4 Checkpoint Inhibition Improves Sepsis Survival in Alcohol-Exposed Mice.ImmunoHorizons · 2024Article
- Combinatorial microRNA Loading into Extracellular Vesicles for Increased Anti-Inflammatory Efficacy.Non-coding RNA · 2022Article
- Expression of CXCR4 on CD4Frontiers in psychiatry · 2022Article
- Comprehensive Analysis of Ferroptosis- and Immune-Related Signatures to Improve the Prognosis and Diagnosis of Kidney Renal Clear Cell Carcinoma.Frontiers in immunology · 2022Article
- PD-L1Nature communications · 2021Article
- IL-33 drives the production of mouse regulatory T cells with enhanced in vivo suppressive activity in skin transplantation.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2021Article
- Inducing Experimental Polymicrobial Sepsis by Cecal Ligation and Puncture.Current protocols in immunology · 2020Article
- Immunotherapy via PD-L1-presenting biomaterials leads to long-term islet graft survival.Science advances · 2020Article
- Histone Deacetylation Inhibitors as Modulators of Regulatory T Cells.International journal of molecular sciences · 2020Review
- Loss of tissue-nonspecific alkaline phosphatase (TNAP) enzyme activity in cerebral microvessels is coupled to persistent neuroinflammation and behavioral deficits in late sepsis.Brain, behavior, and immunity · 2020Article
- Cell-free hemoglobin increases inflammation, lung apoptosis, and microvascular permeability in murine polymicrobial sepsis.PloS one · 2020Article
- Dendritic cells and regulatory T cells expressing CCR4 provide resistance to coxsackievirus B5-induced pancreatitis.Scientific reports · 2019Article
- Regulatory T-cells in acute dengue viral infection.Immunology · 2018Article
- Distinct T-helper cell responses to Staphylococcus aureus bacteremia reflect immunologic comorbidities and correlate with mortality.Critical care (London, England) · 2018Article
- Pre-existing malignancy results in increased prevalence of distinct populations of CD4+ T cells during sepsis.PloS one · 2018Article
- IL-33 contributes to sepsis-induced long-term immunosuppression by expanding the regulatory T cell population.Nature communications · 2017Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Sepsis is a deadly disease characterized by an overwhelming release of inflammatory mediators and the activation of different types of cells. This altered state of cell activation, termed leukocyte reprogramming, contributes to patient outcome. However, the understanding of the process underlying sepsis and the role of regulatory T cells (Tregs) in sepsis remains to be elucidated. In this study, we investigated the role of CCR4, the CCL17/CCL22 chemokine receptor, in the innate and acquired immune responses during severe sepsis and the role of Tregs in effecting the outcome. In contrast with wild-type (WT) mice subjected to cecal ligation and puncture (CLP) sepsis, CCR4-deficient (CCR4-/-) septic mice presented an increased survival rate, significant neutrophil migration toward the infection site, a low bacterial count in the peritoneum, and reduced lung inflammation and serum cytokine levels. Thus, a better early host response may favor an adequate long-term response. Consequently, the CCR4-/- septic mice were not susceptible to secondary fungal infection, in contrast with the WT septic mice. Furthermore, Tregs cells from the CCR4-/- septic mice showed reduced suppressive effects on neutrophil migration (both in vivo and in vitro), lymphocyte proliferation and ROS production from activated neutrophils, in contrast with what was observed for Tregs from the WT septic mice. These data show that CCR4 is involved in immunosuppression after severe sepsis and suggest that CCR4+ Tregs negatively modulate the short and long-term immune responses.
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