Adaptive and innate immune responses in Coeliac Disease

Celiac disease (CD) is a complex small intestinal disorder due to a dysregulated immune response to wheat gliadin and related proteins whichleads to a small intestinal enteropathy. It is generally accepted that CD is a T-cell mediated disease, in which, gliadin derived peptides, eitherin native form or deamidated by tissue transglutaminase, activate lamina propria infiltrating T lymphocytes which release proinflammatorycytokines. Recent studies indicate that gliadin contains also peptides able to activate an innate immune response. In particular, they inducea selective expansion of IEL, particularly TCR/+ and CD8 + TCR /+ lymphocytes bearing the CD94 NK receptor, as well as a strongepithelial expression of MICA molecules which interact with NKG2D receptor expressed on TCR/+ and NK cells. Most of the events ofinnate immune activation events are inhibited by antibodies neutralizing IL-15, thus confirming the key role of this cytokine as a mediator ofintestinal mucosa damage induced by ingestion of gliadin. It remains to be established to what extent the ability of gliadin peptides to activateinnate immunity relates to other biological properties exerted not only on celiac cells and tissues; the specificity of celiac patients is probablyrelated to their genetic make up.