Journal
AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY
Volume 297, Issue 4, Pages R1118-R1126Publisher
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpregu.90904.2008
Keywords
vagus nerve; murine models of colitis; nuclear factor-kappa B; cytokines; regulatory T cells
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Funding
- Science Foundation Ireland
- Health Research Board (HRB) of Ireland
- Higher Education Authority (HEA) of Ireland
- Broad Medical Research Program
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O'Mahony C, van der Kleij H, Bienenstock J, Shanahan F, O'Mahony L. Loss of vagal anti-inflammatory effect: in vivo visualization and adoptive transfer. Am J Physiol Regul Integr Comp Physiol 297: R1118-R1126, 2009. First published August 12, 2009; doi: 10.1152/ajpregu.90904.2008.-The vagus nerve is a conduit for bidirectional signaling between the brain and the viscera. Vagal signaling has been shown to downregulate gastrointestinal inflammation, and the mechanism is thought to involve acetylcholine binding to the alpha-7 subunit of the nicotinic acetylcholine receptor on macrophages. The aims of this study were to quantify the impact of vagotomy in vivo by visualizing nuclear factor (NF)-kappa B activity and to determine if the proinflammatory impact of vagotomy could be transferred by lymphocytes. Real-time biophotonic imaging revealed that subdiaphragmatic vagotomy resulted in increased levels of NF-kappa B in vivo. NF-kappa B activation was further exaggerated in vivo following exposure to 4% DSS for 5 days. Vagotomized animals also exhibited higher disease activity scores and secreted more proinflammatory cytokines. Adoptive transfer of CD4(+) T cells from vagotomized animals (but not CD4(+) T cells from sham-operated controls) to naive dextran sulfate sodium (DSS)-treated recipients resulted in increased inflammatory scores. Further examination of the CD4(+) T cells revealed that adoptive transfer of the CD25(-) population alone from vagotomized donors (but not sham-operated donors) was sufficient to aggravate colitis in DSS-treated recipients. Increased DSS-induced inflammation was associated with reduced CD4(+)CD25(+)Foxp3(+) regulatory T cell numbers in recipients. This study clearly demonstrates the ability of the vagus nerve to modulate activity of the proinflammatory transcription factor NF-kappa B in vivo. The proinflammatory effect of vagotomy is transferable using splenic T cells and highlights a previously unappreciated cellular mechanism for linking central para-sympathetic processes with mucosal inflammation and immune homeostasis.
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