title: Platelets modulate the immune response following trauma by interaction with CD4+ T regulatory cells in a mouse model.
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.
authors.affiliation: Experimental Trauma Surgery, Klinikum rechts der Isar, Technical University Munich, Ismaninger Strasse 22, 81675, Munich, Germany.
authors.forename: Christian B
authors.initials: CB
authors.lastname: Bergmann
authors.affiliation: Experimental Trauma Surgery, Klinikum rechts der Isar, Technical University Munich, Ismaninger Strasse 22, 81675, Munich, Germany.
authors.forename: Friederike
authors.initials: F
authors.lastname: Hefele
authors.affiliation: Experimental Trauma Surgery, Klinikum rechts der Isar, Technical University Munich, Ismaninger Strasse 22, 81675, Munich, Germany.
authors.forename: Marina
authors.initials: M
authors.lastname: Unger
authors.affiliation: Department of Trauma Surgery, Klinikum rechts der Isar, Technical University Munich, Ismaninger Strasse 22, 81675, Munich, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Huber-Wagner
authors.affiliation: Department of Trauma Surgery, Klinikum rechts der Isar, Technical University Munich, Ismaninger Strasse 22, 81675, Munich, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Biberthaler
authors.affiliation: Experimental Trauma Surgery, Klinikum rechts der Isar, Technical University Munich, Ismaninger Strasse 22, 81675, Munich, Germany.
authors.forename: Martijn
authors.initials: M
authors.lastname: van Griensven
authors.affiliation: Experimental Trauma Surgery, Klinikum rechts der Isar, Technical University Munich, Ismaninger Strasse 22, 81675, Munich, Germany. Marc.Hanschen@mri.tum.de.|Department of Trauma Surgery, Klinikum rechts der Isar, Technical University Munich, Ismaninger Strasse 22, 81675, Munich, Germany. Marc.Hanschen@mri.tum.de.
authors.forename: Marc
authors.initials: M
authors.lastname: Hanschen
mesh_terms: D000818:Animals; D015415:Biomarkers; D001792:Blood Platelets / Q000276:immunology* / Q000378:metabolism*; D002056:Burns / Q000276:immunology / Q000378:metabolism; D002450:Cell Communication; D004195:Disease Models, Animal; D006706:Homeostasis; D056747:Immunomodulation; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D051379:Mice; D019007:P-Selectin / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism*; D060149:Tetraspanin 30 / Q000378:metabolism; D051217:Toll-Like Receptor 9 / Q000378:metabolism; D014947:Wounds and Injuries / Q000276:immunology* / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D019007:P-Selectin; D060149:Tetraspanin 30; D051217:Toll-Like Receptor 9
keywords: Adaptive immune response; Cell communication; Hemostasis; Platelets; Regulatory T cells; Trauma