Possible drug targets for celiac disease
- 18 July 2006
- journal article
- review article
- Published by Taylor & Francis in Emerging Therapeutic Targets
- Vol. 10 (4) , 601-611
- https://doi.org/10.1517/14728222.10.4.601
Abstract
Celiac disease (CD) is an intestinal disorder caused by an altered immune response against wheat gluten, a common dietary antigen, and related cereal proteins. Both CD4+ and CD8+ T cells have a role in inducing the intestinal damage, although recent studies have also pinpointed the involvement of the innate immune response in CD pathogenesis. So far, the only available treatment for CD is the strict avoidance of gluten in the diet, but the poor compliance and the associated complications demand alternative therapies. During the last decade, the knowledge of genetic, molecular and cellular mechanisms leading to CD pathogenesis made great progress. The improved understanding of gluten peptides activating either adaptive or innate immune response, of HLA restriction molecules, as well as of cytokines that mediate most of the inflammatory reactions, opens several new promising perspectives for therapeutic intervention. This review discusses both molecular and cellular strategies to treat CD, including the use of proteolytic enzymes active on gluten peptides, antibodies neutralising IL-15 and IFN-γ, drugs targeting HLA, regulatory cytokines and T cells.Keywords
This publication has 77 references indexed in Scilit:
- Limited Efficiency of Prolyl-Endopeptidase in the Detoxification of Gliadin Peptides in Celiac DiseaseGastroenterology, 2005
- Fermentation, purification, formulation, and pharmacological evaluation of a prolyl endopeptidase from Myxococcus xanthus: Implications for Celiac Sprue therapyBiotechnology & Bioengineering, 2005
- Prolyl Endopeptidase-Mediated Destruction of T Cell Epitopes in Whole Gluten: Chemical and Immunological CharacterizationThe Journal of Pharmacology and Experimental Therapeutics, 2005
- Coordinated Induction by IL15 of a TCR-Independent NKG2D Signaling Pathway Converts CTL into Lymphokine-Activated Killer Cells in Celiac DiseaseImmunity, 2004
- Identification of transglutaminase‐mediated deamidation sites in a recombinant α‐gliadin by advanced mass‐spectrometric methodologiesProtein Science, 2003
- Intranasal administration of a recombinant α-gliadin down-regulates the immune response to wheat gliadin in DQ8 transgenic miceImmunology Letters, 2003
- Anatomical basis of tolerance and immunity to intestinal antigensNature Reviews Immunology, 2003
- Gluten specific, HLA-DQ restricted T cells from coeliac mucosa produce cytokines with Th1 or Th0 profile dominated by interferon gamma.Gut, 1995
- Dietary modulation of gluten sensitivity in a naturally occurring enteropathy of Irish setter dogs.Gut, 1992
- Agglutinating activity of gliadin-derived peptides from bread wheat: Implications for coeliac disease pathogenesisBiochemical and Biophysical Research Communications, 1984