title: Nod2 deficiency is associated with an increased mucosal immunoregulatory response to commensal microorganisms.
abstract: On the basis of previous studies demonstrating that a breach of the colonic epithelial barrier is associated with a microbiota-dependent increase in lamina propria (LP) regulatory cells, we investigated if the lack of spontaneous intestinal inflammation observed in nucleotide-binding oligomerization domain 2 (Nod2)-/- mice was due to enhanced intestinal regulatory function. We found that the LP CD4+ T-cell population of Nod2-/- mice contains an increased percentage of CD4+ regulatory T cells bearing transforming growth factor -β/latency peptide (LP CD4+LAP (latency-associated peptide) + T cells) both under baseline conditions and following an intentional breach of the colonic barrier induced by ethanol administration. In addition, we found that Nod2-/- mice manifest decreased severity of 2,4,6-trinitrobenzene sulfonic acid (TNBS)-colitis and that TNBS-colitis in Nod2-/- or Nod2+/+ mice is ameliorated by adoptive transfer of LP cells from ethanol-treated mice before, but not after, depletion of LAP+ T cells. This increased regulatory T-cell response in Nod2-/- mice could explain why NOD2 polymorphisms in humans are not in themselves sufficient to establish inflammatory lesions.
authors: Immune-Mediated Diseases Section, Department of Infectious, Parasitic, and Immune-Mediated Diseases, Rome, Italy.
authors: A
authors: A
authors: Amendola
authors: Immune-Mediated Diseases Section, Department of Infectious, Parasitic, and Immune-Mediated Diseases, Rome, Italy.
authors: A
authors: A
authors: Butera
authors: Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Rome, Italy.
authors: M
authors: M
authors: Sanchez
authors: Mucosal Immunity Section, Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland, USA.
authors: W
authors: W
authors: Strober
authors: Immune-Mediated Diseases Section, Department of Infectious, Parasitic, and Immune-Mediated Diseases, Rome, Italy.
authors: M
authors: M
authors: Boirivant
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D039521:CD11c Antigen / Q000378:metabolism; D003092:Colitis / Q000139:chemically induced / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D003106:Colon / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D056747:Immunomodulation / Q000235:genetics*; D007413:Intestinal Mucosa / Q000276:immunology* / Q000378:metabolism* / Q000382:microbiology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D064307:Microbiota; D053473:Nod2 Signaling Adaptor Protein / Q000172:deficiency*; D010539:Permeability; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism
chemical_list: D039521:CD11c Antigen; D053473:Nod2 Signaling Adaptor Protein
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