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Aberrant extrathymi...
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Bas, AUmeå universitet,Immunologi/immunkemi
(författare)
Aberrant extrathymic T cell receptor gene rearrangement in the small intestinal mucosa : a risk factor for coeliac disease?
- Artikel/kapitelEngelska2009
Förlag, utgivningsår, omfång ...
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2008-02-25
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BMJ,2009
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printrdacarrier
Nummerbeteckningar
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LIBRIS-ID:oai:DiVA.org:umu-21080
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https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-21080URI
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https://doi.org/10.1136/gut.2007.125526DOI
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Språk:engelska
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Sammanfattning på:engelska
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Ämneskategori:ref swepub-contenttype
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Ämneskategori:art swepub-publicationtype
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BACKGROUND: Coeliac disease is a small intestine enteropathy caused by permanent intolerance to wheat gluten. Gluten intake by patients with coeliac disease provokes a strong reaction by intestinal intraepithelial lymphocytes (IELs), which normalises on a gluten-free diet. AIM: To investigate whether impaired extrathymic T cell maturation and/or secondary T cell receptor (TCR) gene recombination in IELs are features of coeliac disease which could contribute to the failure of establishing tolerance to gluten.METHODS: Expression levels of the four splice-forms of recombination activating gene-1 (RAG1) mRNA and preT alpha-chain (preTalpha) mRNA were determined in IEL-subsets of children with coeliac disease and controls. Frequencies of RAG1 expressing IELs were determined by immunomorphometry.RESULTS: In controls, the RAG1-1A/2 splice-form selectively expressed outside the thymus, was dominant and expressed in both mature (TCR(+)) and immature (CD2(+)CD7(+)TCR(-)) IELs ( approximately 8 mRNA copies/18S rRNA U). PreTalpha was expressed almost exclusively in CD2(+)CD7(+)TCR(-) IELs ( approximately 40 mRNA copies/18S rRNA U). By contrast, RAG1 and preTalpha mRNA levels were low in patients with coeliac disease compared to controls, both with active disease and with inactive, symptom-free disease on a gluten-free diet (p values <0.01 for mature and <0.05 for immature IELs). Similarly, the frequencies of RAG1+ IELs were significantly lower in patients with coeliac disease compared to controls (p<0.001).CONCLUSIONS: Patients with coeliac disease appear to have an impaired capacity for extrathymic TCR gene rearrangement. This is an inherent feature, which probably plays a pivotal role in the failure to efficiently downregulate the T cell response to gluten.
Ämnesord och genrebeteckningar
Biuppslag (personer, institutioner, konferenser, titlar ...)
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Forsberg, GUmeå universitet,Immunologi/immunkemi,Pediatrik
(författare)
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Sjöberg, VeronikaUmeå universitet,Immunologi/immunkemi,Hammarström(Swepub:umu)veasjg04
(författare)
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Hammarström, StenUmeå universitet,Immunologi/immunkemi,Hammarström(Swepub:umu)stha0002
(författare)
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Hernell, OlleUmeå universitet,Pediatrik(Swepub:umu)olhe0002
(författare)
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Hammarström, Marie-LouiseUmeå universitet,Immunologi/immunkemi,Hammarström(Swepub:umu)maha0008
(författare)
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Umeå universitetImmunologi/immunkemi
(creator_code:org_t)
Sammanhörande titlar
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Ingår i:Gut: BMJ58:2, s. 189-1950017-57491468-3288
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