T_H17 (and T_H1) 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_H1-dominated group of diseases, where IL-12 induced IFNγ is the major proinflamatory signal. Recently, another linage of T cells has been described, namely T_H17, characterized by production of IL-17, that differentiate in response to TGFβ 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_H1 (IL-12 and IFNγ) and T_H17 (TGFβ, 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_H1 and T_H17 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_H1 and T_H17 promoting factors was observed, suggestive of a reactivation of proinflammatory pathways. These results place CD into the group of autoimmune disorders in which T_H17 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.

• Celiac disease
• intestinal biopsy
• Th17 response
• Th1 response
• interleukins

Acknowledgements

This work was partially funded by Research Project grants 06/111030 from the Basque Department of Health and PI07/0796 from the Instituto de Salud Carlos III of the Spanish Ministry of Health and a Research Award from the Celiac Patient Association from Madrid. Ainara Castellanos-Rubio and Izortze Santín are predoctoral fellows supported by grants from the Spanish Ministry of Education and the University of the Basque Country, respectively. Jose Ramon Bilbao is co-funded by the I3SNS Program of the Spanish Ministry of Health (CES05/036).

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.