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.
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Authors | A Amendola, A Butera, M Sanchez, W Strober, M Boirivant |
Journal | Mucosal immunology
(Mucosal Immunol)
Vol. 7
Issue 2
Pg. 391-404
(Mar 2014)
ISSN: 1935-3456 [Electronic] United States |
PMID | 23962873
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Chemical References |
- CD11c Antigen
- Nod2 Signaling Adaptor Protein
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Topics |
- Adoptive Transfer
- Animals
- CD11c Antigen
(metabolism)
- Colitis
(chemically induced, immunology, metabolism, microbiology)
- Colon
(immunology, metabolism, pathology)
- Dendritic Cells
(immunology, metabolism)
- Immunomodulation
(genetics)
- Intestinal Mucosa
(immunology, metabolism, microbiology)
- Male
- Mice
- Mice, Knockout
- Microbiota
- Nod2 Signaling Adaptor Protein
(deficiency)
- Permeability
- T-Lymphocyte Subsets
(immunology, metabolism)
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