Dataset Information

Valosin-containing protein-regulated endoplasmic reticulum stress causes NOD2-dependent inflammatory responses

ABSTRACT: To detect novel NOD2 interaction partners in the context of IBD, immunoprecipitates from wildtype NOD2 and mutant NOD2 with IBD-causing variants were analyzed using LC-MS/MS.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

SUBMITTER: Thomas Fröhlich

LAB HEAD: Thomas Fröhlich

PROVIDER: PXD031539 | Pride | 2025-03-05

REPOSITORIES: Pride

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Publications

Valosin-containing protein-regulated endoplasmic reticulum stress causes NOD2-dependent inflammatory responses.

Ghalandary Maryam M Li Yue Y Li Yue Y Fröhlich Thomas T Magg Thomas T Liu Yanshan Y Rohlfs Meino M Hollizeck Sebastian S Conca Raffaele R Schwerd Tobias T Uhlig Holm H HH Bufler Philip P Koletzko Sibylle S Muise Aleixo M AM Snapper Scott B SB Hauck Fabian F Klein Christoph C Kotlarz Daniel D

Scientific reports 20220310 1

NOD2 polymorphisms may affect sensing of the bacterial muramyl dipeptide (MDP) and trigger perturbed inflammatory responses. Genetic screening of a patient with immunodeficiency and enteropathy revealed a rare homozygous missense mutation in the first CARD domain of NOD2 (ENST00000300589; c.160G > A, p.E54K). Biochemical assays confirmed impaired NOD2-dependent signaling and proinflammatory cytokine production in patient's cells and heterologous cellular models with overexpression of the NOD2 mu ...[more]

PMID: 35273242

Similar Datasets

Project description:Instability in the composition of gut bacterial communities, referred as dysbiosis, has been associated with important human intestinal disorders such as CrohnM-bM-^@M-^Ys disease and colorectal cancer. Here, we show that dysbiosis coupled to Nod2 or Rip2 deficiency suffices to cause an increased risk for intestinal inflammation and colitis-associated carcinogenesis in mice. Aggravated epithelial lesions and dysplasia upon chemical-induced injury associated with loss of Nod2 or Rip2 can be prevented by antibiotics or anti-IL6R treatment. Nod2-mediated risk for intestinal inflammation and colitis-associated tumorigenesis is communicable through maternally-transmitted microbiota even to wild-type hosts. Disease progression was identified to drive complex NOD2-dependent changes of the colonic-associated microbiota. Reciprocal microbiota transplantation rescues the vulnerability of Nod2-deficient mice to colonic injury. Altogether, our results unveil an unexpected function for NOD2 in shaping a protective assembly of gut microbial communities, providing a rationale for intentional manipulation of genotype-dependent dysbiosis as a causative therapeutic principle in chronic intestinal inflammation. Analysis used RNA extracted from colonic mucosa of untreated, antibiotics-treated or metronidazole-treated C57Bl/6J and Nod2-deficient mice in CAC model. Direct comparisons were performed as follow: C57Bl/6J untreated mice vs Nod2-deficient untreated mice, C57Bl/6J antibiotics-treated mice vs Nod2-deficient antibiotics-treated mice, C57Bl/6J metronidazole-treated mice vs Nod2-deficient metronidazole-treated mice, C57Bl/6J untreated mice vs C57Bl/6J antibiotics-treated mice, C57Bl/6J untreated mice vs C57Bl/6J metronidazole-treated mice, Nod2-deficient untreated mice vs Nod2-deficient antibiotics-treated mice, Nod2-deficient untreated mice vs Nod2-deficient metronidazole-treated mice. Indirect comparisons with control data were made across multiple arrays with raw data pulled from different channels for data analysis.

			Action	DRS
	File_Assignment.csv	Csv
	checksum.txt	Txt
	exp1_IBD_NOD2.wiff	Wiff
	exp1_IBD_NOD2.wiff.scan	Wiff
	exp1_IBD_NOD2_RIP2.wiff	Wiff