Increased regulatory T cells suppress traumatic injury induced inflammation and control adaptive immune cell expansion in an experimental model of burn trauma

Abstract

Abstract Trauma-induced inflammatory dysfunction is a lesser appreciated field of conventional immunology. In fact, traumatic injury is the leading cause of death in the US for people under 44 years old and resultantly disrupts immune homeostasis that puts injured patients at risk for developing opportunistic infections and succumbing to post-injury sepsis. Regulatory T cells (Tregs) are unique cells that contribute to immune balance but play a key role in the undesirable post-trauma immune suppression by repressing important Th-1 type immunity. Interestingly however, several reports demonstrate that Tregs confer a survival advantage in trauma. Therefore, it raises the question, do injured patients with quantitively enhanced Tregs fare better than those with less Tregs? Accordingly, we examined the role of increased Tregs on immune cell subsets in a murine burn-trauma model. C57BL/6 mice were treated with anti-DR3 to increase Tregs before burn trauma. Mice treated with anti-DR3 prior to burn and secondary pseudomonas aeruginosa infection showed improved survival compared with untreated mice. CyTOF analysis revealed burn-injured mice given anti-DR3 showed increased counts of Ki-67+ splenic PMN-MDSCs compared to sham and burn-injured control mice. This corresponded with higher levels of PMN chemoattractants by stimulated splenocytes from burn-injured mice given DR3. Sham and burn-injured mice with higher Tregs also had increased numbers of activated γδ T cells compared to untreated mice, suggesting that these cells are regulated by an increase in Tregs. This study indicates that in trauma, it may be necessary to maintain high Treg levels to alleviate trauma-induced immune dysregulation and restore immune homeostasis.