TY - JOUR
T1 - Platelets modulate the immune response following trauma by interaction with CD4+ T regulatory cells in a mouse model
AU - Bergmann, Christian B.
AU - Hefele, Friederike
AU - Unger, Marina
AU - Huber-Wagner, Stefan
AU - Biberthaler, Peter
AU - van Griensven, Martijn
AU - Hanschen, Marc
N1 - Publisher Copyright:
© 2015, Springer Science+Business Media New York.
PY - 2016/4/1
Y1 - 2016/4/1
N2 - 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.
AB - 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.
KW - Adaptive immune response
KW - Cell communication
KW - Hemostasis
KW - Platelets
KW - Regulatory T cells
KW - Trauma
UR - http://www.scopus.com/inward/record.url?scp=84961186434&partnerID=8YFLogxK
U2 - 10.1007/s12026-015-8726-1
DO - 10.1007/s12026-015-8726-1
M3 - Article
C2 - 26471021
AN - SCOPUS:84961186434
SN - 0257-277X
VL - 64
SP - 508
EP - 517
JO - Immunologic Research
JF - Immunologic Research
IS - 2
ER -