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Peroxisome proliferator-activated receptor-γ and thymic stromal lymphopoietin are involved in the pathophysiology of childhood coeliac disease

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Abstract

Celiac disease (CD) is a chronic autoimmune enteropathy caused by exposure to dietary gluten in genetically predisposed individuals. The transcription factor peroxisome proliferator-activated receptor gamma (PPARγ) was shown to exert protective effects in several immune-mediated disorders. Activation of PPARγ suppressed the expression of thymic stromal lymphopoietin (TSLP), an inducer of proinflammatory cytokines. Since the role of TSLP in gluten-sensitive enteropathy is completely unknown, we investigated the involvement of TSLP and its regulator PPARγ in childhood CD. We collected duodenal biopsy specimens from 19 children with newly diagnosed CD, 6 children with treated CD (gluten-free diet, GFD), and 10 controls. Expression of mRNA and protein levels of PPARγ, TSLP, and TSLP receptor were determined by real-time RT-PCR and Western blot, respectively. Duodenal localization of PPARγ and TSLP was studied by immunohistochemistry. In duodenal mucosa of children with CD, the amount of PPARγ was significantly lower and simultaneously that of TSLP significantly higher compared to controls (p < 0.05). In GFD-treated patients, the levels of PPARγ mRNA and protein were significantly higher while that of TSLP markedly lower compared to newly diagnosed CD (p < 0.05). Immunohistochemistry revealed PPARγ and TSLP expression in lamina propria immune cells and in enterocytes. Low expression of PPARγ and high expression of TSLP in the duodenal mucosa of children with newly diagnosed CD suggest that they are involved in the pathophysiology of CD. We hypothesize that PPARγ may be an inhibitory regulator of TSLP-stimulated inflammatory processes in CD.

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Acknowledgments

We are grateful to Mária Bernáth and Erika Sklánitz Samodai for their excellent technical assistance. This work was supported by Hungarian National Scientific Research Foundation Grant-OTKA-K81117, -84087/2010, -K105530, -PD83431, -PD105361; Lendulet Research Grant-LP2011-008, 2011; TÁMOP 4.2.2. B-10/1-2010-2013. Ádám Vannay and Gábor Veres are holders of the János Bolyai Research grant; this work was supported by the János Bolyai Research Scholarschip of the Hungarian Academy of Sciences.

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The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. MTA-SE, Pediatrics and Nephrology Research Group, Budapest, Hungary

    Erna Sziksz, Tivadar Tulassay & Ádám Vannay

  2. 1st Department of Pediatrics, Semmelweis University, 1083, Budapest,, Bókay J. u. 53-54, Hungary

    Erna Sziksz, Kriszta Molnár, Rita Lippai, Domonkos Pap, Anna Ónody, Apor Veres-Székely, Péter Vörös, Dolóresz Szabó, Gábor Veres, Tivadar Tulassay, Ádám Vannay & András Arató

  3. 2nd Department of Pathology, Semmelweis University, Budapest, Hungary

    Hajnalka Győrffy

Authors
  1. Erna Sziksz
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  2. Kriszta Molnár
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  3. Rita Lippai
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  4. Domonkos Pap
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  9. Hajnalka Győrffy
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  10. Gábor Veres
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  11. Tivadar Tulassay
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  12. Ádám Vannay
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  13. András Arató
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Corresponding author

Correspondence to András Arató.

Additional information

Erna Sziksz and Kriszta Molnár have equally contributed to this work.

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Sziksz, E., Molnár, K., Lippai, R. et al. Peroxisome proliferator-activated receptor-γ and thymic stromal lymphopoietin are involved in the pathophysiology of childhood coeliac disease. Virchows Arch 465, 385–393 (2014). https://doi.org/10.1007/s00428-014-1650-2

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  • DOI: https://doi.org/10.1007/s00428-014-1650-2

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