Role of interferon ? in promoting T helper cell type 1 responses in the small intestine in coeliac disease
Role of interferon ? in promoting T helper cell type 1 responses in the small intestine in coeliac disease
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) alpha , a cytokine capable of promoting IFN-gamma 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-alpha 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-gamma . 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-alpha protein was seen in the duodenal mucosa from untreated CD patients but not in controls. This was associated with marked expression of IFN-gamma protein in CD mucosa. Collectively, these results suggest a role for IFN-alpha in promoting Th1 responses to gluten.
coeliac disease, interferon, small intestine, T helper cell response
425-429
Monteleone, G.
bd762d44-920a-4c7d-afb3-b7a123399e73
Pender, S.L.F.
62528b03-ec42-41bb-80fe-48454c2c5242
Alstead, E.
5991415a-e339-4b09-b031-5b5fd28d8483
Hauer, A.C.
850aa535-e122-4ece-9a56-2f8d43b09848
Lionetti, P.
5f7b9885-b7bc-4834-abee-70238aa842c8
MacDonald, T.T.
171334aa-638a-42b0-99f6-e860e2f0ca45
2001
Monteleone, G.
bd762d44-920a-4c7d-afb3-b7a123399e73
Pender, S.L.F.
62528b03-ec42-41bb-80fe-48454c2c5242
Alstead, E.
5991415a-e339-4b09-b031-5b5fd28d8483
Hauer, A.C.
850aa535-e122-4ece-9a56-2f8d43b09848
Lionetti, P.
5f7b9885-b7bc-4834-abee-70238aa842c8
MacDonald, T.T.
171334aa-638a-42b0-99f6-e860e2f0ca45
Monteleone, G., Pender, S.L.F., Alstead, E., Hauer, A.C., Lionetti, P. and MacDonald, T.T.
(2001)
Role of interferon ? in promoting T helper cell type 1 responses in the small intestine in coeliac disease.
Gut, 48 (3), .
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) alpha , a cytokine capable of promoting IFN-gamma 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-alpha 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-gamma . 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-alpha protein was seen in the duodenal mucosa from untreated CD patients but not in controls. This was associated with marked expression of IFN-gamma protein in CD mucosa. Collectively, these results suggest a role for IFN-alpha in promoting Th1 responses to gluten.
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Published date: 2001
Additional Information:
Case report
Keywords:
coeliac disease, interferon, small intestine, T helper cell response
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Local EPrints ID: 27274
URI: http://eprints.soton.ac.uk/id/eprint/27274
ISSN: 0017-5749
PURE UUID: 5e9cc5da-5c1e-4217-9900-ef95df73a5b3
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Date deposited: 27 Apr 2006
Last modified: 08 Jan 2022 02:53
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Contributors
Author:
G. Monteleone
Author:
E. Alstead
Author:
A.C. Hauer
Author:
P. Lionetti
Author:
T.T. MacDonald
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