The primary defect in experimental ileitis originates from a nonhematopoietic source

Timothy S. Olson, Brian K. Reuter, Kevin G.E. Scott, Margaret A. Morris, Xiao Ming Wang, Leslie N. Hancock, Tracy L. Burcin, Steven Cohn, Peter B. Ernst, Fabio Cominelli, Jonathan B. Meddings, Klaus Ley, Theresa T. Pizarro

Research output: Contribution to journalArticle

127 Citations (Scopus)

Abstract

The initiating etiologic factor in Crohn's disease (CD) remains unclear. SAMP1/YitFc (SAMP) mice develop chronic ileitis similar to human CD. We used bone marrow chimeras to determine if SAMP ileitis results from a primary immunological defect or from dysregulated mucosal immunity secondary to intrinsic, nonhematopoietic (e.g., epithelial) dysfunction. SAMP mice receiving wild-type (AKR) BM developed severe ileitis, whereas SAMP BM did not confer ileitis to WT recipients. WT lymphocytes from reconstituted SAMP mice resembled native SAMP populations in regard to surface phenotype and cytokine production. Ilea from native SAMP mice and SAMP recipients of wild-type BM displayed decreased epithelial barrier resistance ex vivo and increased epithelial permeability in vivo compared to native WT mice and AKR recipients of SAMP BM. This permeability defect preceded the development of ileal inflammation, was present in the absence of commensal bacteria, and was accompanied by altered ileal mRNA expression of the tight junction proteins claudin-2 and occludin. Our results provide evidence that the primary defect conferring ileitis in SAMP mice originates from a nonhematopoietic source. Generation of pathogenic lymphocytes is a consequence of this defect and does not reflect intrinsic proinflammatory leukocyte properties. Decreased barrier function suggests that defects in the epithelium may represent the primary source of SAMP ileitis susceptibility. JEM

Original languageEnglish (US)
Pages (from-to)541-552
Number of pages12
JournalJournal of Experimental Medicine
Volume203
Issue number3
DOIs
StatePublished - Mar 20 2006
Externally publishedYes

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Ileitis
Crohn Disease
Zonula Occludens-2 Protein
Permeability
Claudin-2
Lymphocytes
Inbred AKR Mouse
Occludin
Mucosal Immunity
Ileum
Leukocytes
Epithelium
Bone Marrow
Cytokines
Inflammation
Bacteria
Phenotype
Messenger RNA
Population

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Olson, T. S., Reuter, B. K., Scott, K. G. E., Morris, M. A., Wang, X. M., Hancock, L. N., ... Pizarro, T. T. (2006). The primary defect in experimental ileitis originates from a nonhematopoietic source. Journal of Experimental Medicine, 203(3), 541-552. https://doi.org/10.1084/jem.20050407

The primary defect in experimental ileitis originates from a nonhematopoietic source. / Olson, Timothy S.; Reuter, Brian K.; Scott, Kevin G.E.; Morris, Margaret A.; Wang, Xiao Ming; Hancock, Leslie N.; Burcin, Tracy L.; Cohn, Steven; Ernst, Peter B.; Cominelli, Fabio; Meddings, Jonathan B.; Ley, Klaus; Pizarro, Theresa T.

In: Journal of Experimental Medicine, Vol. 203, No. 3, 20.03.2006, p. 541-552.

Research output: Contribution to journalArticle

Olson, TS, Reuter, BK, Scott, KGE, Morris, MA, Wang, XM, Hancock, LN, Burcin, TL, Cohn, S, Ernst, PB, Cominelli, F, Meddings, JB, Ley, K & Pizarro, TT 2006, 'The primary defect in experimental ileitis originates from a nonhematopoietic source', Journal of Experimental Medicine, vol. 203, no. 3, pp. 541-552. https://doi.org/10.1084/jem.20050407
Olson TS, Reuter BK, Scott KGE, Morris MA, Wang XM, Hancock LN et al. The primary defect in experimental ileitis originates from a nonhematopoietic source. Journal of Experimental Medicine. 2006 Mar 20;203(3):541-552. https://doi.org/10.1084/jem.20050407
Olson, Timothy S. ; Reuter, Brian K. ; Scott, Kevin G.E. ; Morris, Margaret A. ; Wang, Xiao Ming ; Hancock, Leslie N. ; Burcin, Tracy L. ; Cohn, Steven ; Ernst, Peter B. ; Cominelli, Fabio ; Meddings, Jonathan B. ; Ley, Klaus ; Pizarro, Theresa T. / The primary defect in experimental ileitis originates from a nonhematopoietic source. In: Journal of Experimental Medicine. 2006 ; Vol. 203, No. 3. pp. 541-552.
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