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 language | English |
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Pages (from-to) | 137-145 |
Number of pages | 9 |
Journal | Cellular Immunology |
Volume | 331 |
DOIs | |
Publication status | Published - Sept 2018 |
Externally published | Yes |
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