TH17 (and TH1) signatures of intestinal biopsies of CD patients in response to gliadin

Abstract

Celiac disease (CD) is an immunological disorder caused by intolerance to ingested gliadin and other cereal prolamins that has been included in the T(H)1-dominated group of diseases, where IL-12 induced IFNgamma is the major proinflamatory signal. Recently, another linage of T cells has been described, namely T(H)17, characterized by production of IL-17, that differentiate in response to TGFbeta and IL-6 and participate in the pathogenesis of several autoimmune diseases. Using RT-PCR analysis of gene expression, we analyzed the presence of T(H)1 (IL-12 and IFNgamma) and T(H)17 (TGFbeta, IL-6, IL-17A, IL-17F and IL-23) related cytokines in intestinal biopsies from CD patients with active disease compared to remission and from treated patients after acute, in vitro re-exposure to gliadin. Potent T(H)1 and T(H)17 responses were present in the active stage of the disease, whereas short incubation of normalized biopsies with gliadin did not increase the expression of the effector cytokines, although a tendency of upregulation for both T(H)1 and T(H)17 promoting factors was observed, suggestive of a reactivation of proinflammatory pathways. These results place CD into the group of autoimmune disorders in which T(H)17 cells also participate, although the relative importance of each T cell response and their role in the initial events of the disease need further investigation.