Recent advances in gastrointestinal immunology.

Biancheri P et al. Abnormal thymic stromal lymphopoietin expression in the duodenal mucosa of patients with coeliac disease. Gut 2015;0:1-11 The expression of epithelial-derived thymic stromal lymphopoietin (TSLP), a key cytokine modulator of gut immune tolerance, may be dysregulated in coeliac disease (CD). This study investigated TSLP expression along the clinical spectrum of CD and evaluated the ex vivo and in vitro effects of TSLP isoforms in CD mucosa. D2 biopsies from 64 patients with untreated CD, 50 patients with treated CD, 8 patients with refractory CD, 4 patients with potential CD and 43 control subjects were analysed. TSLP gene and protein expression was significantly lower in the epithelium and lamina propria of patients with untreated and refractory CD compared to the control, treated and potential CD groups (p<0.05). This occurred irrespective of the degree of mucosal damage and may be related to the expression of furin, an endopeptidase known to cleave TSLP, which was increased in the D2 mucosa of untreated CD compared with treated CD and controls (p<0.05). TSLP was associated with a number of immunological consequences. Long and short TSLP isomers downregulated the production of pro-inflammatory IFN-γ, IL-8 and T-bet, a Th1specific transcription factor, when cultured with untreated CD biopsies ex vivo (p<0.05). Furthermore IL-8 was significantly decreased in the culture supernatants of treated CD (p<0.005) and controls (p<0.05) compared to untreated CD. Overall TSLP deficiency in active CD may cause upregulation of the Th1 mucosal immune response with subsequent mucosal damage. Restoring TSLP function may represent a novel therapeutic target in patients with refractory CD.