The posttraumatic activation of CD4+ T regulatory cells is modulated by TNFR2- and TLR4-dependent pathways, but not by IL-10

Matthias Bock, Christian B Bergmann, Sonja Jung, Miriam Kalbitz, Borna Relja, Stefan Huber-Wagner, Peter Biberthaler, Martijn van Griensven, Marc Hanschen*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Platelets modulate the immune system following injury by interacting with CD4+ T regulatory cells (CD4+ Tregs). The underlying mechanisms remain unsolved. We hypothesize paracrine interactions via Tumor necrosis factor-alpha (TNFα)-, Toll like receptor-4 (TLR4)-, and Interleukin-10 (IL-10). In the murine burn injury model, CD4+ Treg activation pathways were selectively addressed using TNFR2-, TLR4- and IL-10-deficient mice. The CD4+ Treg signalling molecule PKC-θ was analyzed using phospho-flow cytometry to detect rapid cell activation. Thromboelastometry (ROTEM®) was used to assess platelet activation. Injury induced significant early activation of CD4+ Tregs, disruption of TNFR2 and TLR4 activation pathways resulted in lower activity. The disruption of IL-10 crosstalk had no significant impact. Selective disruption of paracrine interactions is associated with changes in posttraumatic hemostasis parameters. TNFR2- and TLR4-dependent pathways modulate the activation of CD4+ Tregs following trauma. In contrast, we did not observe a role of IL-10 in the posttraumatic activation of CD4+ Tregs.

ONE SENTENCE SUMMARY: TLR4- and TNFR2-dependent mechanisms, but not IL-10-dependent pathways, modulate the anti-inflammatory response of CD4+ Tregs following trauma.

Original languageEnglish
Pages (from-to)137-145
Number of pages9
JournalCellular Immunology
Volume331
DOIs
Publication statusPublished - Sep 2018
Externally publishedYes

Keywords

  • Animals
  • Burns/immunology
  • CD4-Positive T-Lymphocytes/immunology
  • Interleukin-10/genetics
  • Lymphocyte Activation/immunology
  • Male
  • Mice, 129 Strain
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Platelet Activation/immunology
  • Protein Kinase C-theta/immunology
  • Receptors, Tumor Necrosis Factor, Type II/genetics
  • Signal Transduction/genetics
  • T-Lymphocytes, Regulatory/immunology
  • Toll-Like Receptor 4/genetics
  • TOLERANCE
  • INJURY
  • Adaptive immune response
  • CD4(+) T-CELLS
  • Regulatory T cells
  • TNF
  • Hemostasis
  • PLATELETS
  • LOCALIZATION
  • Cell communication
  • Trauma
  • FLOW-CYTOMETRY
  • Platelets
  • EXPRESSION
  • EPIDEMIOLOGY
  • TRAUMA

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