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Diverse FOXP3 Expression in Children with Type 1 Diabetes and Celiac Disease
Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Linköping University, Faculty of Health Sciences.
Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Linköping University, Faculty of Health Sciences.
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2008 (English)In: Annals of the New York Academy of Sciences, ISSN 0077-8923, Vol. 1150, 273-277 p.Article in journal (Refereed) Published
Abstract [en]

Imbalance between different types of T lymphocytes, such as T helper (Th) and regulatory T cells (Tregs), has been reported to play a part in the pathogenesis behind such autoimmune diseases as type 1 diabetes (T1D) and celiac disease (CD). Defects in Tregs are proposed to at least partly explain the imbalance of Th cells found in children with immunologic diseases. Peripheral blood mononuclear cells from 24 children with T1D and/or CD, and reference children (that is, those without any of these diseases) were stimulated with disease-associated antigens (insulin, gluten, transglutaminase [tTG]), and phytohemagglutinin (PHA). The mRNA expression of the Treg-associated marker FOXP3 was analyzed with multiplex real-time RT-PCR. Children with T1D showed both a low spontaneous (P < 0.05) and PHA-induced (P < 0.01) expression of FOXP3 mRNA compared to children with CD. Children with T1D also had a low PHA-induced FOXP3 mRNA expression compared to the group of children diagnosed with both T1D and CD (P < 0.05). Spontaneous (P < 0.05) and PHA-induced (P < 0.05) FOXP3 mRNA expression was high in children with CD compared to reference children. In contrast, stimulation with insulin tended to induce high FOXP3 mRNA expression in T1D children compared to reference children (P = 0.057). In conclusion, children with only T1D generally showed a lower FOXP3 mRNA expression than did children with CD, or with T1D in combination with CD, which suggests impaired regulation of the immune system in children with T1D.

Place, publisher, year, edition, pages
2008. Vol. 1150, 273-277 p.
Keyword [en]
type 1 diabetes, celiac disease, immune regulation, FOXP3
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-16622DOI: 10.1196/annals.1447.018OAI: oai:DiVA.org:liu-16622DiVA: diva2:159535
Note
Volume 1150 Issue: Immunology of Diabetes V From Bench to Bedside.Available from: 2009-02-08 Created: 2009-02-06 Last updated: 2011-11-09
In thesis
1. Combinations of type 1 diabetes, celiac disease and allergy: An immunological challenge
Open this publication in new window or tab >>Combinations of type 1 diabetes, celiac disease and allergy: An immunological challenge
2011 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The immune system is composed of a complex network of different cell types protecting the body against various possible threats. Among these cells are T-helper (Th) cells type 1 (Th1) and type 2 (Th2), as well as T regulatory (Treg) cells. Th1 and Th2 are supposed to be in balance with each other, while Tregs regulate the immune response, by halting it when the desired effect, i.e. destroying the threat, is acquired. However, sometimes this intricate interplay in the immune system is disturbed, leading to diseases as type 1 diabetes (T1D), celiac disease or allergic disease. According to the paradigm claiming that Th1- and Th2-cells inhibit each other a coexistence of a Th1-deviated disease and a Th2-deviated disease seems unlikely.

This thesis aimed to examine the immune response with focus on subsets of T-cells in children with T1D, celiac disease, allergy, or a combination of two of these diseases, in comparison to reference children (healthy).

In line with previous findings we observed that children with celiac disease showed a decreased spontaneous Th2-associated secretion, whereas children with allergic disease showed increased birch- and cat-induced Th2-associated response.

The most remarkable results in this thesis are those observed in children with combinations of diseases. The combination of T1D and celiac disease decreased the Th1-associated response against several antigens, but instead displayed a more pronounced Treg-associated response. Further, in children with combined T1D and allergy an increased Th1- and Th2-associated response was seen to a general stimulus, and an increased birch-induced Th1-, Th2-, Treg- and pro-inflammatory response. In contrast, the combination of allergy and celiac disease showed a decreased spontaneous Th1-, Th2-, Treg- and pro-inflammatory response.

In conclusion, we observed that two Th1-deviated diseases in combination suppress the immune response and increase the regulatory activity. Further it seems that allergy has the ability to shift the immune response in diverging directions depending on which disease it is combined with. The observed suppressive effect might be due to exhaustion of the immune system from the massive pressure of two immunological diseases in combination, while the pronounced Treg response might be caused by an attempt to compensate for the dysfunction. These results shed some light on the intriguing and challenging network that constitutes the immune system, and hopefully give clues regarding disease prevention and treatment.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2011. 109 p.
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1277
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-71915 (URN)978-91-7393-021-5 (ISBN)
Public defence
2011-12-02, Berzeliussalen, Hälsouniversitetet, Campus US, Linköpings universitet, Linköping, 09:00 (Swedish)
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Available from: 2011-11-09 Created: 2011-11-09 Last updated: 2011-11-17Bibliographically approved

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Kivling, AnnaNilsson, LennartFälth-Magnusson, KarinFaresjö, Maria

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Kivling, AnnaNilsson, LennartFälth-Magnusson, KarinFaresjö, Maria
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