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

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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.

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Acknowledgments

The authors thank Fritz Seidl, M.A. translating and interpreting, administration staff of the department, for editing and language revision of this manuscript. This report includes experimental work performed by C.B. Bergmann in fulfillment of his doctoral thesis requirements in the context of the program ‘Translational Medicine.’ This study was supported by grant funding from the Technical University Munich, ‘Kommission fuer Klinische Forschung’ C09-11 (M.H.) and a stipend program ‘Translational Medicine’ (C.B.B.).

Author contributions

C.B.B., M.v.G. and M.H. designed the research; C.B.B., F.H., M.U. and M.H. performed the research; C.B.B., M.v.G. and M.H. performed statistical analysis, C.B.B., S.H.-W., P.B., M.v.G. and M.H. analyzed and interpreted data, and C.B.B. and M.H. wrote the manuscript; all authors reviewed the draft manuscript and approved the final version for submission.

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Authors and Affiliations

  1. Experimental Trauma Surgery, Klinikum rechts der Isar, Technical University Munich, Ismaninger Strasse 22, 81675, Munich, Germany

    Christian B. Bergmann, Friederike Hefele, Marina Unger, Martijn van Griensven & Marc Hanschen

  2. Department of Trauma Surgery, Klinikum rechts der Isar, Technical University Munich, Ismaninger Strasse 22, 81675, Munich, Germany

    Stefan Huber-Wagner, Peter Biberthaler & Marc Hanschen

Authors
  1. Christian B. Bergmann
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  2. Friederike Hefele
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  3. Marina Unger
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  6. Martijn van Griensven
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  7. Marc Hanschen
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Correspondence to Marc Hanschen.

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Bergmann, C.B., Hefele, F., Unger, M. et al. Platelets modulate the immune response following trauma by interaction with CD4+ T regulatory cells in a mouse model. Immunol Res 64, 508–517 (2016). https://doi.org/10.1007/s12026-015-8726-1

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  • DOI: https://doi.org/10.1007/s12026-015-8726-1

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