Wheat Amylase Trypsin Inhibitors as Divers of Innate Immunity in ...
Wheat Amylase Trypsin Inhibitors as Divers of Innate Immunity in ... Wheat Amylase Trypsin Inhibitors as Divers of Innate Immunity in ...
„gluten sensitivity“ without DQ2/8 and celiac auto-Abs Verdu EF et al, Am J Gastroenterol 2009
Role of the Innate Immune System in celiac disease – prior work • Stimulation of biopsies from CD patients with whole gliadin digests or α2 gliadin p31-43 increases the number of IL-15 positive cells within the lamina propria (Maiuri et al, Lancet 2003) • p31-43 induces MICA on intestinal epithelial cells via IL-15, providing a target for cytotoxic IELs (Hue et al, Immunity 2004) • Peptic-tryptic tryptic gliadin digests and certain gliadin peptides induce activation and maturation of monocytes, , macrophages and dendritic cells (Tuckova Tuckova et al, J Leuk Biol 2002; Palova-Jelinkova et al, FEBS Lett 2004; Nikulina et al, J Immunol 2004; Palova-Jelinkova et al. J Immunol., 2005; Cinova et al, J Clin Immunol 2007; Rakhimova et al., J Clin Immunol 2008) • Gliadin increases intestinal permeability and induces DC activation via MyD88 (implication of CXCR3 on intestinal epithelial cells as gliadin receptor) (Thomas et al., J Immunol., 2006; Lammert et al, Gastroenterology 2008) Problems: 1. LPS contamination not strictly ruled out 2. No reproducible identification of a certain (set of) gliadin peptide(s) 3. No receptor identified
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Role <strong>of</strong> the <strong>Innate</strong> Immune System <strong>in</strong> celiac dise<strong>as</strong>e – prior work<br />
• Stimulation <strong>of</strong> biopsies from CD patients with whole gliad<strong>in</strong> digests or α2<br />
gliad<strong>in</strong> p31-43 <strong>in</strong>cre<strong>as</strong>es the number <strong>of</strong> IL-15 positive cells with<strong>in</strong> the lam<strong>in</strong>a<br />
propria<br />
(Maiuri<br />
et al, Lancet 2003)<br />
• p31-43 <strong>in</strong>duces MICA on <strong>in</strong>test<strong>in</strong>al epithelial cells via IL-15, provid<strong>in</strong>g a target<br />
for cytotoxic IELs (Hue et al, <strong>Immunity</strong> 2004)<br />
• Peptic-tryptic<br />
tryptic gliad<strong>in</strong> digests and certa<strong>in</strong> gliad<strong>in</strong> peptides <strong>in</strong>duce activation<br />
and maturation <strong>of</strong> monocytes, , macrophages and dendritic cells (Tuckova<br />
Tuckova et al, J<br />
Leuk Biol 2002; Palova-Jel<strong>in</strong>kova<br />
et al, FEBS Lett 2004; Nikul<strong>in</strong>a et al, J Immunol 2004;<br />
Palova-Jel<strong>in</strong>kova<br />
et al. J Immunol., 2005; C<strong>in</strong>ova et al, J Cl<strong>in</strong> Immunol 2007; Rakhimova et al.,<br />
J Cl<strong>in</strong> Immunol 2008)<br />
• Gliad<strong>in</strong> <strong>in</strong>cre<strong>as</strong>es <strong>in</strong>test<strong>in</strong>al permeability and <strong>in</strong>duces DC activation via MyD88<br />
(implication <strong>of</strong> CXCR3 on <strong>in</strong>test<strong>in</strong>al epithelial cells <strong>as</strong> gliad<strong>in</strong> receptor) (Thom<strong>as</strong><br />
et al., J Immunol., 2006; Lammert et al, G<strong>as</strong>troenterology 2008)<br />
Problems:<br />
1. LPS contam<strong>in</strong>ation not strictly ruled out<br />
2. No reproducible identification <strong>of</strong> a certa<strong>in</strong> (set <strong>of</strong>) gliad<strong>in</strong> peptide(s)<br />
3. No receptor identified