title: Neuroenteric axis modulates the balance of regulatory T cells and T-helper 17 cells in the mesenteric lymph node following trauma/hemorrhagic shock.
abstract: CD103(+) 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(+) 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(+) 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(+) 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.
authors.affiliation: Division of Trauma, Surgical Critical Care, Burns, and Acute Care Surgery, Department of Surgery, University of California San Diego Health Sciences, San Diego, California.
authors.forename: Koji
authors.initials: K
authors.lastname: Morishita
authors.affiliation: Division of Trauma, Surgical Critical Care, Burns, and Acute Care Surgery, Department of Surgery, University of California San Diego Health Sciences, San Diego, California.
authors.forename: Raul
authors.initials: R
authors.lastname: Coimbra
authors.affiliation: Division of Trauma, Surgical Critical Care, Burns, and Acute Care Surgery, Department of Surgery, University of California San Diego Health Sciences, San Diego, California.
authors.forename: Simone
authors.initials: S
authors.lastname: Langness
authors.affiliation: Division of Trauma, Surgical Critical Care, Burns, and Acute Care Surgery, Department of Surgery, University of California San Diego Health Sciences, San Diego, California.
authors.forename: Brian P
authors.initials: BP
authors.lastname: Eliceiri
authors.affiliation: Division of Trauma, Surgical Critical Care, Burns, and Acute Care Surgery, Department of Surgery, University of California San Diego Health Sciences, San Diego, California tcostantini@ucsd.edu.
authors.forename: Todd W
authors.initials: TW
authors.lastname: Costantini
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000276:immunology; D002465:Cell Movement / Q000502:physiology; D003713:Dendritic Cells / Q000276:immunology*; D004195:Disease Models, Animal; D007249:Inflammation / Q000209:etiology / Q000276:immunology*; D039001:Integrin alpha Chains / Q000276:immunology; D007422:Intestines / Q000276:immunology; D008198:Lymph Nodes / Q000378:metabolism*; D008297:Male; D008643:Mesentery; D051381:Rats; D017207:Rats, Sprague-Dawley; D012771:Shock, Hemorrhagic / Q000150:complications / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D058504:Th17 Cells / Q000276:immunology*; D055536:Vagus Nerve Stimulation
chemical_list: D015703:Antigens, CD; D039001:Integrin alpha Chains; C091367:alpha E integrins
keywords: gut inflammation; mesenteric lymph; systemic inflammatory response; vagus nerve