Enterocolitis induced by autoimmune targeting of enteric glial cells: A possible mechanism in Crohn's disease?

Cornet, A; Savidge, Tor; Cabarrocas, Julie; Deng, Wen; Colombel, Jean–Frédéric; Lassmann, Hans; Desreumaux, Pierre; Liblau, Roland

doi:10.1073/pnas.231474098

Cited by 289 publications

(309 citation statements)

References 49 publications

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“…The role that the gut microflora plays in initiating IBD in this model is currently being examined in mice bred in germ-free conditions. An alternative transgenic model, perhaps more relevant to the pathophysiology of IBD, has recently been established that supports the findings in the GFAPHSVtk transgenic mice (Cornet et al, 2001). This model relies on two transgenic mouse lines.…”

Section: Transgenic Mouse Models To Study Egc Pathophysiology and Ibdmentioning

confidence: 71%

“…The fundamental role that EGCs play in maintaining the integrity of the ENS was recently demonstrated in two transgenic mouse models in which the EGCs were specifically killed, leading in both cases to the development of a fulminant and lethal intestinal disease (Bush et al, 1998;Cornet et al, 2001). In both cases, ablation of EGCs led to a breakdown of the epithelium barrier, suggesting a role of EGCs in maintaining the integrity or the permeability of the mucosa.…”

Section: Neuroprotective and Neuromodulatory Functions Of Egcmentioning

confidence: 96%

“…A potential pathophysiological involvement of EGCs in human IBD has recently been suggested by a com-parison of Crohn's disease biopsy samples and the previously described transgenic models (Bush et al, 1998;Cornet et al, 2001). Early pathological manifestations of Crohn's disease include T-cell infiltration of myenteric plexi, enteric neuronal pathology, and vascular disturbances (Wakefield et al, 1991;D'Haens et al, 1998;Geboes and Collins, 1998).…”

Section: Enteric Glial Cells In Human Ibdmentioning

confidence: 99%

“…These observations strongly argue that EGCs can act as antigen-presenting cells. In vivo, EGCs constitutively express MHC class I molecules and can be directly targeted by autoreactive MHC class I-restricted CD8 ϩ T-cells (Cornet et al, 2001). Moreover, EGCs have been shown to express MHC class II in inflammatory conditions such as Crohn's disease (Koretz et al, 1984;Geboes et al, 1992), and electron microscopy analysis of Crohn's disease lesions revealed that infiltrating T-cells could make close contact with MHC class II-expressing EGCs (Geboes et al, 1992).…”

Section: Implication Of Egc In Inflammatory Andmentioning

confidence: 99%

“…In two transgenic mouse models, selective destruction of EGCs led to significantly compromised epithelial and vascular integrity within the gastrointestinal tract, resulting in a fulminating inflammation, hemorrhage, and necrosis (Bush et al, 1998;Cornet et al, 2001). In the first model, transgenic mice were generated to express the herpes simplex virus thymidine kinase gene (HSVtk) under the control of the mouse GFAP promoter (Bush et al, 1998).…”

Section: Transgenic Mouse Models To Study Egc Pathophysiology and Ibdmentioning

confidence: 99%

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Role of enteric glial cells in inflammatory bowel disease

Cabarrocas

Savidge

Liblau

2002

Glia

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154

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Enteric glial cells (EGCs) represent an extensive but relatively poorly described cell population within the gastrointestinal tract. Accumulating data suggest that EGCs represent the morphological and functional equivalent of CNS astrocytes within the enteric nervous system (ENS). The EGC network has trophic and protective functions toward enteric neurons and is fully implicated in the integration and the modulation of neuronal activities. Moreover, EGCs seem to be active elements of the ENS during intestinal inflammatory and immune responses, sharing with astrocytes the ability to act as antigen-presenting cells and interacting with the mucosal immune system via the expression of cytokines and cytokine receptors. Transgenic mouse systems have demonstrated that specific ablation of EGC by chemical ablation or autoimmune T-cell targeting induces an intestinal pathology that shows similarities to the early intestinal immunopathology of Crohn's disease. EGCs may also share with astrocytes the ability to regulate tissue integrity, thereby postulating that similar interactions to those observed for the blood-brain barrier may also be partly responsible for regulating mucosal and vascular permeability in the gastrointestinal tract. Disruption of the EGC network in Crohn's disease patients may represent one possible cause for the enhanced mucosal permeability state and vascular dysfunction that are thought to favor mucosal inflammation. GLIA 41:81-93, 2003.

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Section: Transgenic Mouse Models To Study Egc Pathophysiology and Ibdmentioning

confidence: 71%

Section: Neuroprotective and Neuromodulatory Functions Of Egcmentioning

confidence: 96%

Section: Enteric Glial Cells In Human Ibdmentioning

confidence: 99%

Section: Implication Of Egc In Inflammatory Andmentioning

confidence: 99%

Section: Transgenic Mouse Models To Study Egc Pathophysiology and Ibdmentioning

confidence: 99%

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Role of enteric glial cells in inflammatory bowel disease

Cabarrocas

Savidge

Liblau

2002

Glia

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160

154

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Cytokines and Chemokines in Mucosal Homeostasis

Maillard

Snapper

2010

Inflammatory Bowel Disease

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Enteric Glia: S100, GFAP, and Beyond

Grundmann

Loris

Maas-Omlor

et al. 2019

The Anatomical Record

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Since several years, the enteric nervous system (ENS) is getting more and more in the focus of gastrointestinal research. While the main interest was credited for years to the enteric neurons and their functional properties, less attention has been paid on the enteric glial cells (EGCs). Although the similarity of EGCs to central nervous system (CNS) astrocytes has been demonstrated a long time ago, EGCs were investigated in more detail only recently. Similar to the CNS, there is not "the" EGC, but also a broad range of diversity. Based on morphology and protein expression, such as glial fibrillary acidic protein (GFAP), S100, or Proteolipid-protein-1 (PLP1), several distinct glial types can be differentiated. Their heterogeneity in morphology, localization, and transcription as well as interaction with surrounding cells indicate versatile functional properties of these cells for gut function in health and disease. Although NG2 is found in a subset of CNS glial cells, it did not colocalize with the glial marker S100 or GFAP in the ENS. Instead, it in part colocalize with PDGFRα, as it does in the CNS, which do stain fibroblast-like cells in the gastrointestinal tract. Moreover, there seem to be species dependent differences. While GFAP is always found in the rodent ENS, this is completely different for the human gut.Only the compromised human ENS shows a significant amount of GFAPpositive glial cells. So, in general we can conclude that the EGC population is species specific and as complex as CNS glia. Anat Rec, 302:1333Rec, 302: -1344Rec, 302: , 2019.

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Enterocolitis induced by autoimmune targeting of enteric glial cells: A possible mechanism in Crohn's disease?

Cited by 289 publications

References 49 publications

Role of enteric glial cells in inflammatory bowel disease

Role of enteric glial cells in inflammatory bowel disease

Cytokines and Chemokines in Mucosal Homeostasis

Enteric Glia: S100, GFAP, and Beyond

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