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Targeting Enteric Neurons and Plexitis for the Management of Inflammatory Bowel Disease

[ Vol. 21 , Issue. 14 ]

Author(s):

Rhian Stavely, Raquel Abalo and Kulmira Nurgali*   Pages 1428 - 1439 ( 12 )

Abstract:


Ulcerative colitis (UC) and Crohn’s disease (CD) are pathological conditions with an unknown aetiology that are characterised by severe inflammation of the intestinal tract and collectively referred to as inflammatory bowel disease (IBD). Current treatments are mostly ineffective due to their limited efficacy or toxicity, necessitating surgical resection of the affected bowel. The management of IBD is hindered by a lack of prognostic markers for clinical inflammatory relapse. Intestinal inflammation associates with the infiltration of immune cells (leukocytes) into, or surrounding the neuronal ganglia of the enteric nervous system (ENS) termed plexitis or ganglionitis. Histological observation of plexitis in unaffected intestinal regions is emerging as a vital predictive marker for IBD relapses. Plexitis associates with alterations to the structure, cellular composition, molecular expression and electrophysiological function of enteric neurons. Moreover, plexitis often occurs before the onset of gross clinical inflammation, which may indicate that plexitis can contribute to the progression of intestinal inflammation. In this review, the bilateral relationships between the ENS and inflammation are discussed. These include the effects and mechanisms of inflammation-induced enteric neuronal loss and plasticity. Additionally, the role of enteric neurons in preventing antigenic/pathogenic insult and immunomodulation is explored. While all current treatments target the inflammatory pathology of IBD, interventions that protect the ENS may offer an alternative avenue for therapeutic intervention.

Keywords:

Enteric nervous system, inflammatory bowel disease, Crohn’s disease, ulcerative colitis, neuro-immune, inflammation, plexitis, neuroprotection.

Affiliation:

Department of Pediatric Surgery, Pediatric Surgery Research Laboratories, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, Área de Farmacología y Nutrición, Departamento de Ciencias Básicas de la Salud, Universidad Rey Juan Carlos (URJC), 28922 Alcorcón, Institute for Health and Sport, Victoria University; Western Centre for Health, Research and Education, Sunshine Hospital, Melbourne, Victoria



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