Regulatory T-cell Function is Impaired in Celiac Disease

Overview

Journal Dig Dis Sci

Specialty Gastroenterology

Date 2008 Nov 1

PMID 18975083

Citations 25

Authors

Marilena Granzotto

Sara Dal Bo

Sara Quaglia

Alberto Tommasini

Elisa Piscianz

Erica Valencic

Fortunato Ferrara

Stefano Martelossi

Alessandro Ventura

Tarcisio Not

Affiliations

Soon will be listed here.

Abstract

Celiac disease (CD) is characterized by intolerance to gluten and high risk of developing autoimmune phenomena. Possible defects in immune tolerance could have a role in the pathogenesis of the disease. As regulatory T-cells (Tregs) are the main population involved in maintaining peripheral tolerance, we investigated the number of these cells in celiac patients as compared with healthy donors. Moreover, we analyzed the suppressive function of CD4+CD25+ T-cells from celiac disease patients and controls on autologous responder T-cells (CD4+CD25-). The percentage of CD4+CD25+FOXP3+ cells was not different in celiacs and in healthy controls, and among positive cells the level of expression of the two regulatory markers was comparable. However, the suppressor activity of Tregs was significantly impaired in CD patients. These results suggest that a defect in Tregs function could play a role in the pathogenesis of CD and in CD-associated autoimmunity.

Citing Articles

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References

Allan S, Crome S, Crellin N, Passerini L, Steiner T, Bacchetta R . Activation-induced FOXP3 in human T effector cells does not suppress proliferation or cytokine production. Int Immunol. 2007; 19(4):345-54. DOI: 10.1093/intimm/dxm014. View

Gianfrani C, Levings M, Sartirana C, Mazzarella G, Barba G, Zanzi D . Gliadin-specific type 1 regulatory T cells from the intestinal mucosa of treated celiac patients inhibit pathogenic T cells. J Immunol. 2006; 177(6):4178-86. DOI: 10.4049/jimmunol.177.6.4178. View

Collin P, Maki M . Associated disorders in coeliac disease: clinical aspects. Scand J Gastroenterol. 1994; 29(9):769-75. DOI: 10.3109/00365529409092508. View

Wildin R, Ramsdell F, Peake J, Faravelli F, Casanova J, Buist N . X-linked neonatal diabetes mellitus, enteropathy and endocrinopathy syndrome is the human equivalent of mouse scurfy. Nat Genet. 2001; 27(1):18-20. DOI: 10.1038/83707. View

Wan Y, Flavell R . Identifying Foxp3-expressing suppressor T cells with a bicistronic reporter. Proc Natl Acad Sci U S A. 2005; 102(14):5126-31. PMC: 556008. DOI: 10.1073/pnas.0501701102. View

Schuppan D . Current concepts of celiac disease pathogenesis. Gastroenterology. 2000; 119(1):234-42. DOI: 10.1053/gast.2000.8521. View

Baecher-Allan C, Viglietta V, Hafler D . Inhibition of human CD4(+)CD25(+high) regulatory T cell function. J Immunol. 2002; 169(11):6210-7. DOI: 10.4049/jimmunol.169.11.6210. View

Kriegel M, Lohmann T, Gabler C, Blank N, Kalden J, Lorenz H . Defective suppressor function of human CD4+ CD25+ regulatory T cells in autoimmune polyglandular syndrome type II. J Exp Med. 2004; 199(9):1285-91. PMC: 2211900. DOI: 10.1084/jem.20032158. View

Bennett C, Christie J, Ramsdell F, Brunkow M, Ferguson P, Whitesell L . The immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome (IPEX) is caused by mutations of FOXP3. Nat Genet. 2001; 27(1):20-1. DOI: 10.1038/83713. View

10.

Abdulahad W, Stegeman C, van der Geld Y, Doornbos-van der Meer B, Limburg P, Kallenberg C . Functional defect of circulating regulatory CD4+ T cells in patients with Wegener's granulomatosis in remission. Arthritis Rheum. 2007; 56(6):2080-91. DOI: 10.1002/art.22692. View

11.

. An autoimmune disease, APECED, caused by mutations in a novel gene featuring two PHD-type zinc-finger domains. Nat Genet. 1997; 17(4):399-403. DOI: 10.1038/ng1297-399. View

12.

Marie J, Letterio J, Gavin M, Rudensky A . TGF-beta1 maintains suppressor function and Foxp3 expression in CD4+CD25+ regulatory T cells. J Exp Med. 2005; 201(7):1061-7. PMC: 2213134. DOI: 10.1084/jem.20042276. View

13.

Venken K, Hellings N, Thewissen M, Somers V, Hensen K, Rummens J . Compromised CD4+ CD25(high) regulatory T-cell function in patients with relapsing-remitting multiple sclerosis is correlated with a reduced frequency of FOXP3-positive cells and reduced FOXP3 expression at the single-cell level. Immunology. 2007; 123(1):79-89. PMC: 2433271. DOI: 10.1111/j.1365-2567.2007.02690.x. View

14.

Green P, Cellier C . Celiac disease. N Engl J Med. 2007; 357(17):1731-43. DOI: 10.1056/NEJMra071600. View

15.

Ventura A, Magazzu G, Greco L . Duration of exposure to gluten and risk for autoimmune disorders in patients with celiac disease. SIGEP Study Group for Autoimmune Disorders in Celiac Disease. Gastroenterology. 1999; 117(2):297-303. DOI: 10.1053/gast.1999.0029900297. View

16.

Sakaguchi S, Sakaguchi N, Asano M, Itoh M, Toda M . Immunologic self-tolerance maintained by activated T cells expressing IL-2 receptor alpha-chains (CD25). Breakdown of a single mechanism of self-tolerance causes various autoimmune diseases. J Immunol. 1995; 155(3):1151-64. View

17.

Not T, Tommasini A, Tonini G, Buratti E, Pocecco M, Tortul C . Undiagnosed coeliac disease and risk of autoimmune disorders in subjects with Type I diabetes mellitus. Diabetologia. 2001; 44(2):151-5. DOI: 10.1007/s001250051593. View

18.

Brusko T, Atkinson M . Treg in type 1 diabetes. Cell Biochem Biophys. 2007; 48(2-3):165-75. DOI: 10.1007/s12013-007-0018-5. View

19.

Anderson M, Venanzi E, Klein L, Chen Z, Berzins S, Turley S . Projection of an immunological self shadow within the thymus by the aire protein. Science. 2002; 298(5597):1395-401. DOI: 10.1126/science.1075958. View

20.

Tiittanen M, Westerholm-Ormio M, Verkasalo M, Savilahti E, Vaarala O . Infiltration of forkhead box P3-expressing cells in small intestinal mucosa in coeliac disease but not in type 1 diabetes. Clin Exp Immunol. 2008; 152(3):498-507. PMC: 2453216. DOI: 10.1111/j.1365-2249.2008.03662.x. View