P01 – Vagus nerve signaling modulates the balance between regulatory T cells and T-helper 17 cells in the mesenteric lymph node following trauma/hemorrhagic shock

Author(s):
Koji Morishita, Raul Coimbra, Vishal Bansal, Brian Eliceiri, Todd Costantini, UC San Diego Health System

Background: Dendritic cells (DCs) migrate from the gut to the mesenteric lymph node (MLN) and coordinate the response to injury. CD103+ DCs maintain tolerance by driving the development of regulatory T cells (Treg) in the MLN. Treg cells maintain homeostasis by suppressing excessive immune responses, while effector T-helper (Th) 17 cells drive a pro-inflammatory response. The relative expression of Treg and Th17 cells in the gut determine the balance between tolerance and immunity. We have shown that vagus nerve signaling (VNS) prevents gut injury and alters the DC profile in the mesenteric lymph after trauma/hemorrhagic shock (T/HS).

Hypothesis: We hypothesized that 1) T/HS would decrease the CD103+ DC population in the MLN and alter the balance between Treg and Th17 cells, and 2) that VNS would promote tolerance to inflammation by increasing the Treg/Th17 ratio in the MLN after injury.

Methods: Male rats were assigned to trauma/sham shock (T/SS) or T/HS. T/HS was induced by laparotomy and 60 min of HS followed by resuscitation. A cohort of animals underwent cervical VNS following HS. MLN samples were collected 24 hours after resuscitation. For flow cytometric analysis, MLN cells were stained with CD103, MHCII, CD4, CD25, Foxp3, IL-17A, and P-NFKB p65 antibodies.

Results: The CD103+MHCII+ DC population in the MLN was decreased after T/HS and demonstrated increased P-NFKB p65 expression. The Treg/Th17 cell ratio in the MLN was decreased after T/HS compared with T/SS suggesting a shift to an inflammatory response. VNS prevented the T/HS-induced decrease in MLN CD103+ DCs with P-NFKB p65 expression similar to T/SS. VNS increased the Treg/Th17 ratio compared to T/HS alone (*p<0.05).

Conclusions: VNS alters the immune response by altering the balance between Treg and Th17 cells in the MLN. The vagus nerve promotes tolerance to inflammation in the gut further supporting its ability to modulate the injury response.