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Gut. Mar 2001; 48(3): 425–429.
PMCID: PMC1760133

Role of interferon α in promoting T helper cell type 1 responses in the small intestine in coeliac disease

Abstract

Coeliac disease (CD) is caused by a CD4 T helper cell type 1 (Th1) response in the small intestinal mucosa to dietary gluten. As the major Th1 inducing cytokine, interleukin 12, is undetectable in CD gut mucosa, the mechanism by which Th1 effector cells are generated remains unknown. Interferon (IFN) α, a cytokine capable of promoting IFN-γ synthesis, has been implicated in the development of Th1 mediated immune diseases. Here we report a case of CD-like enteropathy in a patient receiving IFN-α for chronic myeloid leukaemia. Morphological assessment of duodenal biopsies taken from the patient showed total villous atrophy, crypt cell hyperplasia, and a high number of CD3+ intraepithelial lymphocytes. Both antigliadin antibodies and antiendomysial antibodies were positive. RNA analysis revealed pronounced expression of IFN-γ. Withdrawal of gluten from the diet resulted in a patchy improvement in intestinal morphology, normalisation of laboratory parameters, and resolution of clinical symptoms. By western blot analysis, IFN-α protein was seen in the duodenal mucosa from untreated CD patients but not in controls. This was associated with marked expression of IFN-γ protein in CD mucosa. Collectively, these results suggest a role for IFN-α in promoting Th1 responses to gluten.


Keywords: coeliac disease; interferon; small intestine; T helper cell response

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Figures and Tables

Figure 1
Frozen sections of duodenal biopsies taken from the patient receiving interferon α therapy before (top) and after (bottom) commencing a gluten free diet. Before the gluten free diet, the mucosa is flat, there is a dense infiltrate of ...
Figure 2
(Top) Southern blot analysis of transcripts for interferon (IFN) γ and β-actin in duodenal mucosal tissue homogenates from three normal controls, three untreated patients with coeliac disease (CD), and the patient with chronic ...

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