Peroxisome proliferator-activated receptor-gamma and thymic stromal lymphopoietin are involved in the pathophysiology of childhood coeliac disease.

Abstract

Celiac disease (CD) is a chronic autoimmune enteropathy caused by exposure to dietary gluten in genetically predisposed individuals. The transcription factor peroxisome proliferator-activated receptor gamma (PPARgamma) was shown to exert protective effects in several immune-mediated disorders. Activation of PPARgamma suppressed the expression of thymic stromal lymphopoietin (TSLP), an inducer of proinflammatory cytokines. Since the role of TSLP in gluten-sensitive enteropathy is completely unknown, we investigated the involvement of TSLP and its regulator PPARgamma in childhood CD. We collected duodenal biopsy specimens from 19 children with newly diagnosed CD, 6 children with treated CD (gluten-free diet, GFD), and 10 controls. Expression of mRNA and protein levels of PPARgamma, TSLP, and TSLP receptor were determined by real-time RT-PCR and Western blot, respectively. Duodenal localization of PPARgamma and TSLP was studied by immunohistochemistry. In duodenal mucosa of children with CD, the amount of PPARgamma was significantly lower and simultaneously that of TSLP significantly higher compared to controls (p < 0.05). In GFD-treated patients, the levels of PPARgamma mRNA and protein were significantly higher while that of TSLP markedly lower compared to newly diagnosed CD (p < 0.05). Immunohistochemistry revealed PPARgamma and TSLP expression in lamina propria immune cells and in enterocytes. Low expression of PPARgamma and high expression of TSLP in the duodenal mucosa of children with newly diagnosed CD suggest that they are involved in the pathophysiology of CD. We hypothesize that PPARgamma may be an inhibitory regulator of TSLP-stimulated inflammatory processes in CD.