Post by kickingfrog on Jan 23, 2017 17:08:32 GMT
Coeliac disease: a unique model for investigating broken tolerance in autoimmunity
Posted by Tracey on 23/1/2017
GF board
www.ncbi.nlm.nih.gov/pmc/articles/PMC5133362/pdf/cti201658a.pdf
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Coeliac disease: a unique model for investigating
broken tolerance in autoimmunity
Melinda Y et al...
Coeliac disease, a prevalent immune-mediated enteropathy driven by dietary gluten, provides an exceptional human model to
dissect the genetic, environmental and immunologic factors operating in autoimmunity. Despite the causative antigen being an
exogenous food protein, coeliac disease has many features in common with autoimmune disease including a strong HLA class II
association and the presence of pathogenic CD4+ T cells and autoantibodies. CD8+ intraepithelial lymphocytes specifically target
and destroy intestinal epithelium in response to stress signals and not a specific antigen. A unique feature of coeliac disease is
the ability to remove gluten to induce disease remission and reintroduce it to trigger a memory response. This provides an
unparalleled opportunity to study disease-relevant CD4+ T cells that have been expanded in vivo. As a result, the causative
peptides have been characterised at a level unprecedented for any autoimmune disease. Despite the complexity of the gluten
proteome, resistance to gastrointestinal proteolysis and susceptibility to post-translational modification by transglutaminase help
shape a restricted repertoire of immunogenic gluten peptides that have high affinity for disease-associated HLA. The critical
steps in coeliac disease pathogenesis have been broadly elucidated and provide the basis for experimental therapies in
pre-clinical or clinical development.
However, little is known about how and why tolerance to gluten sometimes breaks or fails to develop.
Understanding the interactions between genes, the environment, gluten immunity and the microbiome may provide
novel approaches for the prevention and treatment of disease.
Clinical & Translational Immunology (2016) 5, e112; doi:10.1038/cti.2016.58; published online 2 November 2016
www.ncbi.nlm.nih.gov/pmc/articles/PMC5133362/pdf/cti201658a.pdf
Posted by Tracey on 23/1/2017
GF board
www.ncbi.nlm.nih.gov/pmc/articles/PMC5133362/pdf/cti201658a.pdf
*************************
Coeliac disease: a unique model for investigating
broken tolerance in autoimmunity
Melinda Y et al...
Coeliac disease, a prevalent immune-mediated enteropathy driven by dietary gluten, provides an exceptional human model to
dissect the genetic, environmental and immunologic factors operating in autoimmunity. Despite the causative antigen being an
exogenous food protein, coeliac disease has many features in common with autoimmune disease including a strong HLA class II
association and the presence of pathogenic CD4+ T cells and autoantibodies. CD8+ intraepithelial lymphocytes specifically target
and destroy intestinal epithelium in response to stress signals and not a specific antigen. A unique feature of coeliac disease is
the ability to remove gluten to induce disease remission and reintroduce it to trigger a memory response. This provides an
unparalleled opportunity to study disease-relevant CD4+ T cells that have been expanded in vivo. As a result, the causative
peptides have been characterised at a level unprecedented for any autoimmune disease. Despite the complexity of the gluten
proteome, resistance to gastrointestinal proteolysis and susceptibility to post-translational modification by transglutaminase help
shape a restricted repertoire of immunogenic gluten peptides that have high affinity for disease-associated HLA. The critical
steps in coeliac disease pathogenesis have been broadly elucidated and provide the basis for experimental therapies in
pre-clinical or clinical development.
However, little is known about how and why tolerance to gluten sometimes breaks or fails to develop.
Understanding the interactions between genes, the environment, gluten immunity and the microbiome may provide
novel approaches for the prevention and treatment of disease.
Clinical & Translational Immunology (2016) 5, e112; doi:10.1038/cti.2016.58; published online 2 November 2016
www.ncbi.nlm.nih.gov/pmc/articles/PMC5133362/pdf/cti201658a.pdf