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- Document type:
- Article; Journal Article
- Author(s):
- Rupp, Marco-Christopher; Bergmann, Christian Benjamin; Jung, Sonja; Bock, Matthias; Biberthaler, Peter; Heimann, Laura; Hanschen, Marc
- Title:
- The posttraumatic response of CD4+ regulatory T cells is modulated by direct cell-cell contact via CD40L- and P-selectin-dependent pathways.
- Abstract:
- CD4+ FoxP3+ regulatory T cells (CD4+ Tregs) are important for the posttraumatic anti-inflammatory host response. As described previously, platelets are able to modulate CD4+ Treg activity in a reciprocally activating interaction following injury. The underlying mechanisms of the posttraumatic interaction between platelets and CD4+ Tregs remain unclear. We investigated the potential influence of CD40L and P-selectin, molecules known to be involved in direct cell contact of these cell types. In a murine burn injury model, the potential interaction pathways were addressed using CD40L- and P-selectin-deficient mice. Draining lymph nodes were harvested following trauma (1 h) and following a sham procedure. Early rapid activation of CD4+ Tregs was assessed by phospho-flow cytometry (signaling molecules (p)PKC-δ and (p)ZAP-70). Platelet function was analyzed performing rotational thromboelastometry (ROTEM). We hypothesized that disruption of the direct cell-cell contact via CD40L and P-selectin would affect posttraumatic activation of CD4+ Tregs and influence the hemostatic function of platelets. Indeed, while injury induced early activation of CD4+ Tregs in wild-type mice (ZAP-70: p = 0.13, pZAP-70: p < 0.05, PKC-δ: p < 0.05, pPKC-δ: p < 0.05), disruption of CD40L-dependent interaction (ZAP-70: p = 0.57, pZAP-70: p = 0.68, PKC-δ: p = 0.68, pPKC-δ: p = 0.9) or P-selectin-dependent interaction (ZAP-70: p = 0.78, pZAP-70: p = 0.58, PKC-δ: p = 0.81, pPKC-δ: p = 0.73) resulted in reduced posttraumatic activation. Furthermore, hemostatic function was impaired towards hypocoagulability in either deficiency. Our results suggest that the posttraumatic activation of CD4+ Tregs and hemostatic function of platelets are affected by direct cell-cell-signaling via CD40L and P-selectin.
- Journal title abbreviation:
- Cent Eur J Immunol
- Year:
- 2021
- Journal volume:
- 46
- Journal issue:
- 3
- Pages contribution:
- 283-294
- Fulltext / DOI:
- doi:10.5114/ceji.2021.109171
- Pubmed ID:
- http://view.ncbi.nlm.nih.gov/pubmed/34764800
- Print-ISSN:
- 1426-3912
- TUM Institution:
- Klinik und Poliklinik für Unfallchirurgie
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