Defects in mucosal immunity leading to Crohn's disease

Gena M. Cobrin, Maria T Abreu

Research output: Contribution to journalArticle

144 Citations (Scopus)

Abstract

Crohn's disease (CD) is characterized by patchy transmural inflammation involving any part of the intestinal tract. Animal models have provided a great deal of insight into the pathogenesis of CD, but no animal model has recapitulated the full spectrum of manifestations witnessed in human disease. The defects in mucosal immunity in CD can be divided into those that involve the epithelial barrier, those that involve the innate immune response, and finally, defects in the adaptive immune response. Defects in the epithelial barrier in CD include an increase in intestinal permeability, increased adherence of bacteria, and decreased expression of defensins. Murine and human studies have demonstrated an increased expression of T-helper 1 (Th1) cytokines by lamina propria lymphocytes. This increased Th1 cytokine expression is driven by interleukin-12 (IL-12)/IL-23 and tumor necrosis factor-like 1A (TL1A) production by antigen-presenting cells, resulting in Tbet expression by CD4+ T cells. Another dimension of the inappropriate immune response in CD is T-cell and B-cell reactivity to luminal microbes. With the identification of the nucleotide-binding oligomerization domain 2 (NOD2) gene as a susceptibility gene, defects in the innate immune response are beginning to be explored. One may consider a model in which defective innate immune clearance of pathogens or commensal bacteria in CD leads to an inappropriate adaptive immune response to the commensal flora.

Original languageEnglish
Pages (from-to)277-295
Number of pages19
JournalImmunological Reviews
Volume206
DOIs
StatePublished - Aug 1 2005
Externally publishedYes

Fingerprint

Mucosal Immunity
Crohn Disease
Adaptive Immunity
Innate Immunity
Animal Models
Cytokines
Bacteria
Defensins
Interleukin-23
T-Lymphocytes
Antigen-Presenting Cells
Interleukin-12
Genes
Permeability
Mucous Membrane
B-Lymphocytes
Nucleotides
Tumor Necrosis Factor-alpha
Lymphocytes
Inflammation

ASJC Scopus subject areas

  • Immunology

Cite this

Defects in mucosal immunity leading to Crohn's disease. / Cobrin, Gena M.; Abreu, Maria T.

In: Immunological Reviews, Vol. 206, 01.08.2005, p. 277-295.

Research output: Contribution to journalArticle

@article{708a8946fe28454e8fd84534f2320bd8,
title = "Defects in mucosal immunity leading to Crohn's disease",
abstract = "Crohn's disease (CD) is characterized by patchy transmural inflammation involving any part of the intestinal tract. Animal models have provided a great deal of insight into the pathogenesis of CD, but no animal model has recapitulated the full spectrum of manifestations witnessed in human disease. The defects in mucosal immunity in CD can be divided into those that involve the epithelial barrier, those that involve the innate immune response, and finally, defects in the adaptive immune response. Defects in the epithelial barrier in CD include an increase in intestinal permeability, increased adherence of bacteria, and decreased expression of defensins. Murine and human studies have demonstrated an increased expression of T-helper 1 (Th1) cytokines by lamina propria lymphocytes. This increased Th1 cytokine expression is driven by interleukin-12 (IL-12)/IL-23 and tumor necrosis factor-like 1A (TL1A) production by antigen-presenting cells, resulting in Tbet expression by CD4+ T cells. Another dimension of the inappropriate immune response in CD is T-cell and B-cell reactivity to luminal microbes. With the identification of the nucleotide-binding oligomerization domain 2 (NOD2) gene as a susceptibility gene, defects in the innate immune response are beginning to be explored. One may consider a model in which defective innate immune clearance of pathogens or commensal bacteria in CD leads to an inappropriate adaptive immune response to the commensal flora.",
author = "Cobrin, {Gena M.} and Abreu, {Maria T}",
year = "2005",
month = "8",
day = "1",
doi = "10.1111/j.0105-2896.2005.00293.x",
language = "English",
volume = "206",
pages = "277--295",
journal = "Immunological Reviews",
issn = "0105-2896",
publisher = "Wiley-Blackwell",

}

TY - JOUR

T1 - Defects in mucosal immunity leading to Crohn's disease

AU - Cobrin, Gena M.

AU - Abreu, Maria T

PY - 2005/8/1

Y1 - 2005/8/1

N2 - Crohn's disease (CD) is characterized by patchy transmural inflammation involving any part of the intestinal tract. Animal models have provided a great deal of insight into the pathogenesis of CD, but no animal model has recapitulated the full spectrum of manifestations witnessed in human disease. The defects in mucosal immunity in CD can be divided into those that involve the epithelial barrier, those that involve the innate immune response, and finally, defects in the adaptive immune response. Defects in the epithelial barrier in CD include an increase in intestinal permeability, increased adherence of bacteria, and decreased expression of defensins. Murine and human studies have demonstrated an increased expression of T-helper 1 (Th1) cytokines by lamina propria lymphocytes. This increased Th1 cytokine expression is driven by interleukin-12 (IL-12)/IL-23 and tumor necrosis factor-like 1A (TL1A) production by antigen-presenting cells, resulting in Tbet expression by CD4+ T cells. Another dimension of the inappropriate immune response in CD is T-cell and B-cell reactivity to luminal microbes. With the identification of the nucleotide-binding oligomerization domain 2 (NOD2) gene as a susceptibility gene, defects in the innate immune response are beginning to be explored. One may consider a model in which defective innate immune clearance of pathogens or commensal bacteria in CD leads to an inappropriate adaptive immune response to the commensal flora.

AB - Crohn's disease (CD) is characterized by patchy transmural inflammation involving any part of the intestinal tract. Animal models have provided a great deal of insight into the pathogenesis of CD, but no animal model has recapitulated the full spectrum of manifestations witnessed in human disease. The defects in mucosal immunity in CD can be divided into those that involve the epithelial barrier, those that involve the innate immune response, and finally, defects in the adaptive immune response. Defects in the epithelial barrier in CD include an increase in intestinal permeability, increased adherence of bacteria, and decreased expression of defensins. Murine and human studies have demonstrated an increased expression of T-helper 1 (Th1) cytokines by lamina propria lymphocytes. This increased Th1 cytokine expression is driven by interleukin-12 (IL-12)/IL-23 and tumor necrosis factor-like 1A (TL1A) production by antigen-presenting cells, resulting in Tbet expression by CD4+ T cells. Another dimension of the inappropriate immune response in CD is T-cell and B-cell reactivity to luminal microbes. With the identification of the nucleotide-binding oligomerization domain 2 (NOD2) gene as a susceptibility gene, defects in the innate immune response are beginning to be explored. One may consider a model in which defective innate immune clearance of pathogens or commensal bacteria in CD leads to an inappropriate adaptive immune response to the commensal flora.

UR - http://www.scopus.com/inward/record.url?scp=23344431535&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=23344431535&partnerID=8YFLogxK

U2 - 10.1111/j.0105-2896.2005.00293.x

DO - 10.1111/j.0105-2896.2005.00293.x

M3 - Article

C2 - 16048555

AN - SCOPUS:23344431535

VL - 206

SP - 277

EP - 295

JO - Immunological Reviews

JF - Immunological Reviews

SN - 0105-2896

ER -