The imbalance between regulatory and IL-17-secreting CD4+T cells in multiple-trauma rat

Dai, He-ling; Sun, Tiansheng; Li, Zhi; Zhang, Jianzheng; Zhou, Meng

doi:10.1016/j.injury.2013.03.015

Cited by 24 publications

(19 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Interestingly, our results are comparable to data obtained from a trauma model in rats consisting of a bilateral femoral fracture and hemorrhagic shock [47]. Four hours after trauma induction, the number of CD4 + CD25 +/high FoxP3 + Tregs in peripheral blood was significantly lower compared to controls.…”

Section: Discussionsupporting

confidence: 87%

Regulatory T Cells Modulate CD4 Proliferation after Severe Trauma via IL-10

Sturm

Xanthopoulos

Heftrig

et al. 2020

JCM

View full text Add to dashboard Cite

Objective: Severely injured patients frequently develop an immunological imbalance following the traumatic insult, which might result in infectious complications evoked by a persisting immunosuppression. Regulatory T cells (Tregs) maintain the immune homeostasis by suppressing proinflammatory responses, however, their functionality after trauma is unclear. Here, we characterized the role of Tregs in regulating the proliferation of CD4+ lymphocytes in traumatized patients (TP). Methods: Peripheral blood was obtained daily from 29 severely injured TP (Injury Severity Score, ISS ≥16) for ten days following admission to the emergency department (ED). Ten healthy volunteers (HV) served as controls. The frequency and activity of Tregs were assessed by flow cytometry. Proliferation of CD4+ cells was analyzed either in presence or absence of Tregs, or after blocking of either IL-10 or IL-10R1. Results: The frequencies of CD4+CD25high and CD4+CD25+CD127− Tregs were significantly decreased immediately upon admission of TP to the ED and during the following 10 post-injury days. Compared with HV CD4+ T cell proliferation in TP increased significantly upon their admission and on the following days. As expected, CD4+CD25+CD127− Tregs reduced the proliferation of CD4+ cells in HV, nevertheless, CD4+ proliferation in TP was increased by Tregs. Neutralization of IL-10 as well as blocking the IL-10R1 increased further CD4+ T cell proliferation in Tregs-depleted cultures, thereby confirming an IL-10-mediated mechanism of IL-10-regulated CD4+ T cell proliferation. Neutralization of IL-10 in TP decreased CD4+ T cell proliferation in Tregs-depleted cultures, whereas blocking of the IL-10R1 receptor had no significant effects. Conclusions: The frequency of Tregs in the CD4+ T lymphocyte population is reduced after trauma; however, their inductiveness is increased. The mechanisms of deregulated influence of Tregs on CD4+ T cell proliferation are mediated via IL-10 but not via the IL-10R1.

show abstract

Section: Discussionsupporting

confidence: 87%

Regulatory T Cells Modulate CD4 Proliferation after Severe Trauma via IL-10

Sturm

Xanthopoulos

Heftrig

et al. 2020

JCM

View full text Add to dashboard Cite

show abstract

“…Naïve CD4 ϩ T cells can be differentiated into various subsets, such as Th1, Th2, Th17, and Treg cells (9). While the Th1-Th2 paradigm provided a reasonable basis for exploration of the mechanisms of immunity to infection and autoimmune diseases, several lines of evidence suggest that Th1 cells are not the only T cell subset responsible for the induction and progression of immune responses, as originally proposed (24).…”

Section: Discussionmentioning

confidence: 99%

“…Th17 cells have a proinflammatory role and, because they produce IL-17, have been implicated in many inflammatory conditions in humans and mice (25,26,38). Therefore, the Treg-Th17 cell balance is thought to be essential for maintaining immune homeostasis and has long been thought to be one of the important factors in development of the gut inflammatory response (9,24).…”

mentioning

confidence: 99%

Neuroenteric axis modulates the balance of regulatory T cells and T-helper 17 cells in the mesenteric lymph node following trauma/hemorrhagic shock

Coimbra

Langness

Eliceiri

et al. 2015

American Journal of Physiology-Gastrointestinal and Liver Physi

View full text Add to dashboard Cite

Morishita K, Coimbra R, Langness S, Eliceiri BP, Costantini TW. Neuroenteric axis modulates the balance of regulatory T cells and T-helper 17 cells in the mesenteric lymph node following trauma/hemorrhagic shock. Am J Physiol Gastrointest Liver Physiol 309: G202-G208, 2015. First published June 4, 2015 doi:10.1152 doi:10. /ajpgi.00097.2015 ϩ dendritic cells (DCs) continuously migrate from the intestine to the mesenteric lymph nodes (MLNs) and maintain tolerance by driving the development of regulatory T cells (Treg) in the gut. The relative expression of Treg and T-helper 17 (Th17) cells determines the balance between tolerance and immunity in the gut. We hypothesized that trauma/hemorrhagic shock (T/HS) would decrease the CD103 ϩ DC population in the mesenteric lymph and alter the Treg-to-Th17 ratio in the MLN. We further hypothesized that vagus nerve stimulation (VNS) would promote tolerance to inflammation by increasing the Treg-to-Th17 ratio in the MLN after injury. Male rats were assigned to sham shock (SS), trauma/sham shock (T/SS), or T/HS. T/HS was induced by laparotomy and 60 min of HS (blood pressure 35 mmHg) followed by fluid resuscitation. A separate cohort of animals underwent cervical VNS after the HS phase. MLN samples were collected 24 h after resuscitation. The CD103 ϩ DC population and Treg-to-Th17 cell ratio in the MLN were decreased after T/HS compared with SS and T/SS, suggesting a shift to an inflammatory response. VNS prevented the T/HS-induced decrease in the CD103 ϩ DC population and increased the Treg-to-Th17 ratio compared with T/HS alone. VNS alters the gut inflammatory response to injury by modulating the Treg-Th17 cell balance in the MLN. VNS promotes tolerance to inflammation in the gut, further supporting its ability to modulate the inflammatory set point and alter the response to injury. vagus nerve; gut inflammation; mesenteric lymph; systemic inflammatory response

show abstract

“…Furthermore, the damaged tissue and pathogen exposure can result in a ‘toxic’ lymph fluid that flows into the venous system, which leads to deformability of red blood cells, tissue injury, sepsis and MODS, as postulated by the gut-lymph-MODS hypothesis 167–170 . Thus, the balance of adaptive T H 17 cells and regulatory T cells (T reg cells) in immunity and tolerance tilts toward a pro-inflammatory immune response 171,172 . In addition, the neuroenteric axis 173 seems to diminish the abundance of dendritic cells in the mesenteric lymph nodes and thereby tips the T H 17 cell/T reg cell balance after trauma and or hemorrhagic shock.…”

Section: Posttraumatic Immune Response and Breakdown Of Protective Cementioning

confidence: 99%

Innate immune responses to trauma

2018

View full text Add to dashboard Cite

Trauma can affect any individual at any location and at any time over a lifespan. The disruption of macrobarriers and microbarriers induces instant activation of innate immunity. The subsequent complex response, designed to limit further damage and induce healing, also represents a major driver of complications and fatal outcome after injury. This Review aims to provide basic concepts about the posttraumatic response and is focused on the interactive events of innate immunity at frequent sites of injury: the endothelium at large, and sites within the lungs, inside and outside the brain and at the gut barrier.

show abstract

The imbalance between regulatory and IL-17-secreting CD4+T cells in multiple-trauma rat

Cited by 24 publications

References 43 publications

Regulatory T Cells Modulate CD4 Proliferation after Severe Trauma via IL-10

Regulatory T Cells Modulate CD4 Proliferation after Severe Trauma via IL-10

Neuroenteric axis modulates the balance of regulatory T cells and T-helper 17 cells in the mesenteric lymph node following trauma/hemorrhagic shock

Innate immune responses to trauma

Contact Info

Product

Resources

About