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

Abstract

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

Vagotomy Affects the Development of Oral Tolerance and Increases Susceptibility to Develop Colitis Independently of α-7 Nicotinic Receptor

“…On the contrary, to data reported in postoperative ileus and sepsis, α7nAChR was not involved Treg-to-Th17 ratio in MLNs in a rat model of trauma/hemorrhagic shock (27). Although our results support the hypothesis that the vagus nerve plays a role in the maintenance of intestinal immune homeostasis, VGX did not influence severity of T cell transfer model of chronic colitis.…”

Modulating the Biologic Activity of Mesenteric Lymph after Traumatic Shock Decreases Systemic Inflammation and End Organ Injury

“…These findings are in agreement with previous work by our lab and others, where VNS is capable of altering the biologic activity of ML [32, 33, 61]. While the exact mechanism has yet to be determined, VNS appears to alter the inflammatory response of resident gut macrophages as one potential mechanism for its anti-inflammatory effect [62].…”

Innate immune responses to trauma

“…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.…”

“…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. The effect of the trauma-induced ‘toxic lymph’ 167 and shift in the ratio of T H 17 cells to T reg cells can be counterbalanced by stimulation of the vagal nerve 172 . In particular, CD63 + HSP70 + exosomes within the mesenteric lymph nodes represent a major trigger for the monocyte-macrophage pro-inflammatory response 174 .…”