ArticleImmunology2015
Relevance of Foxp3⁺ regulatory T cells for early and late phases of murine sepsis.
Article in Immunology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 50 citations in OpenAlex.
- Serum CCL1 discriminates infectious and sterile systemic inflammation in sepsis and acute pancreatitis.Scientific reports · 2026Article
- GSTP1 as a novel protective target in sepsis: evidence from proteome-wide Mendelian randomization and multi-omics analyses.BMC infectious diseases · 2026Article
- Regulatory B cells attenuate sepsis-associated pancreatic injury by regulating T cell homeostasis.Scientific reports · 2025Article
- Dysregulated Immune Responses in Sepsis: Insights From Treg-Related Gene Expression.Journal of inflammation research · 2025Article
- Th17/Treg balance: the bloom and wane in the pathophysiology of sepsis.Frontiers in immunology · 2024Review
- CD8+ Regulatory T Cells Induced by Lipopolysaccharide Improve Mouse Endotoxin Shock.ImmunoHorizons · 2023Article
- The immunomodulation role of Th17 and Treg in renal transplantation.Frontiers in immunology · 2023Review
- Orally Administered Brain Protein Combined With Probiotics Increases Treg Differentiation to Reduce Secondary Inflammatory Damage Following Craniocerebral Trauma.Frontiers in immunology · 2022Article
- Regulatory T Cells: Angels or Demons in the Pathophysiology of Sepsis?Frontiers in immunology · 2022Review
- Insight Into Regulatory T Cells in Sepsis-Associated Encephalopathy.Frontiers in neurology · 2022Review
- HDL and persistent inflammation immunosuppression and catabolism syndrome.Current opinion in lipidology · 2021Review
- Asthma and COVID-19: a dangerous liaison?Asthma research and practice · 2021Review
- Targeting Neuropilin-1 Suppresses the Stability of CD4Infection and immunity · 2021Article
- Immune Intervention in Sepsis.Frontiers in pharmacology · 2021Review
- Role of the adaptive immune response in sepsis.Intensive care medicine experimental · 2020Review
- COVID-19 and Asthma: Reflection During the Pandemic.Clinical reviews in allergy & immunology · 2020Review
- Glycolytic and lipid oxidative metabolic programs are essential for freshly-isolated regulatory T cells in mice with sepsis.RSC advances · 2020Article
- 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
- Development of Quantitative Methylation-Specific Droplet Digital PCR (ddMSP) for Assessment of Natural Tregs.Frontiers in genetics · 2020Article
- CD4 T Cell Responses and the Sepsis-Induced Immunoparalysis State.Frontiers in immunology · 2020Review
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The role of Foxp3(+) regulatory T (Treg) cells in the course of the early hyper-inflammatory and subsequent hypo-inflammatory phases of sepsis is ambiguous. Whereas Nrp1 expression has been reported to discriminate natural Treg cells from induced Treg cells, the Treg cell stability depends on the methylation status of foxp3-TSDR. To specifically evaluate the role of Foxp3(+) Treg cells in the early and late phases of sepsis, we induced sepsis by caecal ligation and puncture and subsequent Pseudomonas aeruginosa lung infection in a DEREG (DEpletion of REGulatory T cells) mouse model. We found an increase of Foxp3(+) Treg cells to all CD4(+) T cells during murine sepsis. Using a new methylation-sensitive quantitative RT-PCR method and deep amplicon sequencing, we demonstrated that natural (Nrp1(+) Foxp3(+) ) Treg cells and most induced (Nrp1(-) Foxp3(+) ) Treg cells are stable and exhibit unmethylated foxp3-TSDR, and that both Treg populations are functionally suppressive in healthy and septic mice. DEREG mice depleted of Foxp3(+) Treg cells exhibit higher disease scores, mortality rates and interleukin-6 expression levels than do non-depleted DEREG mice in early-phase sepsis, a finding indicating that Foxp3(+) Treg cells limit the hyper-inflammatory response and accelerate recovery. Treg cell depletion before secondary infection with P. aeruginosa 1 week after caecal ligation and puncture does not influence cytokine levels or the course of secondary infection. However, a moderate Treg cell recurrence, which we observed in DEREG mice during secondary infection, may interfere with these results. In summary, Treg cells contribute to a positive outcome after early-phase sepsis, but the data do not support a significant role of Treg cells in immune paralysis during late-phase sepsis.
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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.