Toll-Like Receptor 2 Regulates Intestinal Inflammation by Controlling Integrity of the Enteric Nervous System

The glial cell-line derived neurotrophic factor: a novel regulator of intestinal barrier function in health and disease

“…In recent years it was consistently reported, that reduced levels of GDNF lead to morphological and functional abnormalities of IEB in mice comparable to the changes known in IBD (8,61,68). Conversely, it was shown that GNDF immunoreactivity was upregulated in experimental colitis and in specimen of patients with IBD, which was an effect predominately observed in enterocytes (52).…”

“…The intestinal barrier was restored by the application of GDNF in this study. The underlying mechanism was attributed to a reconstitutive effect of GDNF on the ENS rather than on direct effects of GDNF on the intestinal epithelium (8). Fig.…”

Emerging roles of gut microbiota and the immune system in the development of the enteric nervous system

“…Interestingly, TLR2 polymorphisms have been identified in certain cases of IBD, although the relevance of this finding to the pathogenesis of Crohn's disease or ulcerative colitis remains unclear (114). Enteric neurons and glia also express TLR2 and the myenteric ganglia of Tlr2 -/-mice contained fewer neurons compared with their wild-type counterparts, with the reduction in inhibitory nNOS + neurons being the most notable phenotype (115). The reduction in nNOS + neurons was accompanied by intestinal dysmotility and impaired chloride secretion by ileal explants.…”

Building a second brain in the bowel

“…In IBS, altered bowel motility and sensory responses cause pain accompanied by diarrhea or constipation, but health is not otherwise affected. ENS defects also occur in Parkinson's disease (8), diabetes (9), and inflammatory bowel disease (IBD) (10), and recent data suggest that ENS damage might play an early etiologic role in IBD (11,12) and Parkinson's disease (13)(14)(15). Here, we focus on cellular and molecular mechanisms controlling ENS development, highlighting areas that require further investigation and potential clinical implications of new discoveries.…”