Enteric Murine Ganglionitis Induced by Autoimmune CD8 T Cells Mimics Human Gastrointestinal Dysmotility

Sánchez‐Ruiz, Monica; Brunn, Anna; Montesinos‐Rongen, Manuel; Rudroff, Claudia; Hartmann, Melanie; Schlüter, Dirk; Pfitzer, Gabriele; Deckert, Martina

doi:10.1016/j.ajpath.2018.11.016

Cited by 9 publications

(6 citation statements)

References 36 publications

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“…Recipient mice developed transient GI dysmotility, indicating that dysautonomia in recipient mice mimicked an antibody-mediated pathogenesis for AAG. Sanchez-Ruiz et al reported CD8 T cell-mediated enteric murine ganglionitis [59]. Based on the high prevalence of bowel dysmotility in patients with inflammatory bowel disease, transgenic mice expressing ovalbumin on enteric neurons were generated via induction of severe enteric ganglionitis after adoptive transfer of ovalbumin-specific CD8 T cells.…”

Section: Autoantibodies (Aabs)mentioning

confidence: 99%

Autoimmune gastrointestinal dysmotility: the interface between clinical immunology and neurogastroenterology

Nakane

Mukaino

Ihara

et al. 2020

Immunological Medicine

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Autoimmune gastrointestinal dysmotility (AGID), an idiopathic or paraneoplastic phenomenon, is a clinical form of limited autoimmune dysautonomia. The symptoms of AGID and gastrointestinal manifestations in patients with autoimmune rheumatic diseases are overlapping. Antineuronal autoantibodies are often detected in patients with AGID. Autoantibodies play a key role in GI dysmotility; however, whether they cause neuronal destruction is unknown. Hence, the connection between the presence of these autoantibodies and the specific interference in synaptic transmission in the plexus ganglia of the enteric nervous system has to be determined. The treatment options for AGID are not well-defined. However, theoretically, immunomodulatory therapies have been shown to be effective and are therefore used as the first line of treatment. Nonetheless, diverse combined immunomodulatory therapies should be considered for intractable cases of AGID. We recommend comprehensive autoimmune evaluation and cancer screening for clinical diagnosis of AGID. Univocal diagnostic criteria, treatment protocols, and outcome definitions for AGID are required for prompt diagnosis and treatment and appropriate management of immunotherapy, which will circumvent the need for surgeries and improve patient outcome. In conclusion, AGID, a disease at the interface of clinical immunology and neurogastroenterology, requires further investigations and warrants cooperation among specialists, especially clinical immunologists, gastroenterologists, and neurologists.

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Section: Autoantibodies (Aabs)mentioning

confidence: 99%

Autoimmune gastrointestinal dysmotility: the interface between clinical immunology and neurogastroenterology

Nakane

Mukaino

Ihara

et al. 2020

Immunological Medicine

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“…1 Furthermore, immune infiltration into the MP in IBDs has been shown to preferentially target ganglia. 51,52 It is therefore plausible that intraganglionic EGCs might play a role in the preferential recruitment of immune cells observed in IBDs, as EGCs are known to communicate directly with immune cells. 36,53 Our finding that Gpr37 is restricted to intraganglionic EGCs of the MP and regulates key features of LPS-induced EGC reactive gliosis, including immune cell recruitment, provides compelling evidence for the inflammatory role of intraganglionic EGCs.…”

Section: Discussionmentioning

confidence: 99%

Gpr37 modulates the severity of inflammation-induced GI dysmotility by regulating enteric reactive gliosis

Robertson,

Hahn,

Robinson

et al. 2024

Preprint

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The enteric nervous system (ENS) is contained within two layers of the gut wall and is made up of neurons, immune cells, and enteric glia cells (EGCs) that regulate gastrointestinal (GI) function. EGCs in both inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS) change in response to inflammation, referred to as reactive gliosis. Whether EGCs restricted to a specific layer or region within the GI tract alone can influence intestinal immune response is unknown. Using bulk RNA-sequencing and in s itu hybridization, we identify G-protein coupled receptor Gpr37, as a gene expressed only in EGCs of the myenteric plexus, one of the two layers of the ENS. We show that Gpr37 contributes to key components of LPS-induced reactive gliosis including activation of NF-kB and IFN-y signaling and response genes, lymphocyte recruitment, and inflammation-induced GI dysmotility. Targeting Gpr37 in EGCs presents a potential avenue for modifying inflammatory processes in the ENS.

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“…In another interesting study on autoimmune mechanism-mediated gastrointestinal dysmotility, Sanchez-Ruiz et al investigated CD8 + T cell-mediated enteric murine ganglionitis. 28 Based on the high prevalence of bowel dysmotility in patients with inflammatory bowel disease, transgenic mice expressing ovalbumin on enteric neurons were generated by induction of severe enteric ganglionitis after adoptive transfer of ovalbumin-specific CD8 + T cells. A total of 24 h after the onset of colitis-related symptoms, 60% of the submucosal and myenteric plexus neurons were lost, resulting in severely impaired GI transit.…”

Section: Mouse Models Of Aag Induced By Immunizationmentioning

confidence: 99%

“…Lennon et al, 8 Vernino et al, 9 Tajzoy et al 26 Vernino et al 10 Meeusen et al 27 Sanchez-Ruiz et al 28 Yamakawa et al 32 Year 2003, 8 such as decreased heart rate (HR) and systolic blood pressure (SBP) instability, especially in the third to fifth week, and such dysfunction was also observed from weeks 9 to 11. Poor body weight (BW) gain was confirmed at weeks 3 and 4.…”

Section: Studymentioning

confidence: 99%

“…Based on these results, they considered the possibility that the gastrointestinal hypomotility was not caused by neuronal cell death, but by the internalization and degradation of nicotinic AChRα3s cross‐linked at the neuronal plasma membranes by circulating IgG. In another interesting study on autoimmune mechanism‐mediated gastrointestinal dysmotility, Sanchez‐Ruiz et al investigated CD8 + T cell‐mediated enteric murine ganglionitis 28 . Based on the high prevalence of bowel dysmotility in patients with inflammatory bowel disease, transgenic mice expressing ovalbumin on enteric neurons were generated by induction of severe enteric ganglionitis after adoptive transfer of ovalbumin‐specific CD8 + T cells.…”

Section: Autoantibodies Against Gachr In Mouse Models Of Aagmentioning

confidence: 99%

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Autoantibodies against gAChR in humans and mouse models of autoimmune autonomic ganglionopathy

Nakane,

Yamakawa,

Nakatsuji

2024

Clinical & Exp Neuroim

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The ganglionic nicotinic acetylcholine receptor (gAChR) mediates fast synaptic transmission in all peripheral autonomic ganglia (sympathetic, parasympathetic, and enteric). Over the last two decades, evidence has accumulated for a role of autoantibodies against gAChR in the development of autoimmune autonomic ganglionopathy (AAG). In this review we provide an updated overview of the field, with a highlight on the role of autoimmunity against gAChR in the pathogenesis of AAG. Clinical data as well as findings from experimental disease models are summarized in sections focusing on the presence of autoantibodies against gAChR in patients with AAG, the function of gAChR antibodies, the association of antibodies against gAChR with AAG‐related phenotypes, the in vivo pathogenicity of transferred autoantibodies against gAChR in mice, and mouse models of the disease induced by immunization with the nicotinic AChR. Based on a comprehensive assessment of the currently available data, we propose a hypothetical model for the role of autoantibodies against gAChR in the pathogenesis of AAG.

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Enteric Murine Ganglionitis Induced by Autoimmune CD8 T Cells Mimics Human Gastrointestinal Dysmotility

Cited by 9 publications

References 36 publications

Autoimmune gastrointestinal dysmotility: the interface between clinical immunology and neurogastroenterology

Autoimmune gastrointestinal dysmotility: the interface between clinical immunology and neurogastroenterology

Gpr37 modulates the severity of inflammation-induced GI dysmotility by regulating enteric reactive gliosis

Autoantibodies against gAChR in humans and mouse models of autoimmune autonomic ganglionopathy

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