Platelets modulate the immune response following trauma by interaction with CD4+ T regulatory cells in a mouse model

Christian B Bergmann, Friederike Hefele, Marina Unger, Stefan Huber-Wagner, Peter Biberthaler, Martijn van Griensven, Marc Hanschen*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

CD4+ T regulatory cells (Tregs) play a pivotal role in the anti-inflammatory immune response following trauma. The mechanisms of CD4+ Treg activation are mostly unknown. Here, we hypothesize that platelets regulate CD4+ Treg activation following trauma. In a murine burn injury model (male C57Bl/6N mice), depletion of platelets or CD4+ Tregs was conducted. Draining lymph nodes, blood and spleen were harvested 2 h and 7 days after trauma. CD4+ Treg activation was measured using phospho- and conventional flow cytometry. Platelet activation was analyzed using thromboelastometry and flow cytometry. Trauma differentially activates CD4+ T cells, early after trauma only CD4+ Tregs are activated. Following burn injury, platelets augment the activation of CD4+ Tregs. This effect could only be seen early after trauma. While CD4+ Tregs influence hemostasis early following trauma, platelet activation markers were unchanged. Beyond their role in hemostasis, platelets are able to modulate the immunologic host response to trauma-induced injury by augmenting the activation of CD4+ Tregs. CD4+ Treg activation following trauma is considered protective. In addition, CD4+ Tregs are capable of modulating the hemostatic function of platelets. For the first time, we could show reciprocal activation of platelets and CD4+ Tregs as part of the protective immune response following trauma.

Original languageEnglish
Pages (from-to)508-517
Number of pages10
JournalImmunologic Research
Volume64
Issue number2
DOIs
Publication statusPublished - Apr 2016
Externally publishedYes

Keywords

  • Animals
  • Biomarkers
  • Blood Platelets/immunology
  • Burns/immunology
  • Cell Communication
  • Disease Models, Animal
  • Homeostasis
  • Immunomodulation
  • Lymphocyte Activation/immunology
  • Male
  • Mice
  • P-Selectin/metabolism
  • T-Lymphocyte Subsets/immunology
  • T-Lymphocytes, Regulatory/immunology
  • Tetraspanin 30/metabolism
  • Toll-Like Receptor 9/metabolism
  • Wounds and Injuries/immunology
  • INJURY
  • Adaptive immune response
  • CD4(+) T-CELLS
  • DEPLETION
  • Regulatory T cells
  • NEUTROPHIL EXTRACELLULAR TRAPS
  • Hemostasis
  • PSEUDOMONAS-AERUGINOSA
  • BLOOD
  • Cell communication
  • SEPSIS
  • Trauma
  • INFLAMMATION
  • Platelets
  • CRITICALLY-ILL PATIENTS
  • PKC-THETA

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