title: Gastrointestinal microbiota do not significantly contribute to T cell activation or GI inflammation in Ndfip1-cKO mice.
abstract: The bacteria inhabiting the mammalian gastrointestinal (GI) tract play a vital role in normal digestion and immune function. In a healthy host, the immune system is tolerant to gut bacteria and does not mount an effector response to bacteria-derived antigens. Loss of tolerance to intestinal microflora has been associated with inflammatory bowel disease (IBD) in both mice and humans. Mice lacking Ndfip1, an adaptor protein for E3 ubiquitin ligases of the Nedd4-family, in T cells (Ndfip1-cKO) develop a disease resembling IBD. Inflammation in these mice is characterized by increased activation of peripheral T cells, infiltration of eosinophils into the GI tract, and epithelial hypertrophy in the esophagus. We hypothesized that this intestinal inflammation in Ndfip1-cKO mice is caused by a loss of T-cell tolerance to bacterial antigens. Here, we show that treatment of Ndfip1-cKO mice with broad-spectrum antibiotics drastically reduced bacterial load in stool but had little effect on T-cell activation and did not affect eosinophil infiltration into the GI tract or epithelial hypertrophy in the esophagus. Thus, inflammation in Ndfip1-cKO mice is not caused by a loss of tolerance to intestinal microbiota. Rather, T cell activation and eosinophilia may instead be triggered by other environmental antigens.
authors.affiliation: Cell and Molecular Biology Group, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Kurzweil
authors.forename: Amy
authors.initials: A
authors.lastname: Tarangelo
authors.forename: Paula M
authors.initials: PM
authors.lastname: Oliver
mesh_terms: D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology / Q000378:metabolism; D001419:Bacteria / Q000276:immunology / Q000378:metabolism; D058491:Bacterial Load / Q000276:immunology; D002352:Carrier Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D056827:Endosomal Sorting Complexes Required for Transport / Q000276:immunology / Q000378:metabolism; D004804:Eosinophils / Q000276:immunology / Q000378:metabolism; D005260:Female; D041981:Gastrointestinal Tract / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology* / Q000503:physiopathology; D007108:Immune Tolerance / Q000276:immunology; D007249:Inflammation / Q000276:immunology / Q000378:metabolism / Q000382:microbiology* / Q000503:physiopathology; D015212:Inflammatory Bowel Diseases / Q000276:immunology / Q000382:microbiology / Q000503:physiopathology; D036341:Intercellular Signaling Peptides and Proteins; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000276:immunology / Q000382:microbiology / Q000503:physiopathology; D008213:Lymphocyte Activation / Q000276:immunology*; D008565:Membrane Proteins / Q000172:deficiency / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D054892:Metagenome / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D000075702:Nedd4 Ubiquitin Protein Ligases; D011247:Pregnancy; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000276:immunology / Q000378:metabolism
chemical_list: D000942:Antigens, Bacterial; D002352:Carrier Proteins; D056827:Endosomal Sorting Complexes Required for Transport; D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C499188:Ndfip1 protein, mouse; D000075702:Nedd4 Ubiquitin Protein Ligases; C000618483:Nedd4 protein, human; C000618461:Nedd4l protein, mouse; D044767:Ubiquitin-Protein Ligases