IL-21 production by CD4+ effector T cells and frequency of circulating follicular helper T cells are increased in type 1 diabetes patients

Autor: Ferreira, Ricardo C., Simons, Henry Z., Thompson, Whitney S., Cutler, Antony J., Dopico, Xaquin Castro, Smyth, Deborah J., Mashar, Meghavi, Schuilenburg, Helen, Walker, Neil M., Dunger, David B., Wallace, Chris, Todd, John A., Wicker, Linda S., Pekalski, Marcin L.
Přispěvatelé: Dunger, David [0000-0002-2566-9304], Wallace, Chris [0000-0001-9755-1703], Apollo - University of Cambridge Repository
Jazyk: angličtina
Rok vydání: 2015
Předmět:
Zdroj: Diabetologia
ISSN: 1432-0428
0012-186X
Popis: Aims/hypothesis Type 1 diabetes results from the autoimmune destruction of insulin-secreting pancreatic beta cells by T cells. Despite the established role of T cells in the pathogenesis of the disease, to date, with the exception of the identification of islet-specific T effector (Teff) cells, studies have mostly failed to identify reproducible alterations in the frequency or function of T cell subsets in peripheral blood from patients with type 1 diabetes. Methods We assessed the production of the proinflammatory cytokines IL-21, IFN-γ and IL-17 in peripheral blood mononuclear cells from 69 patients with type 1 diabetes and 61 healthy donors. In an additional cohort of 30 patients with type 1 diabetes and 32 healthy donors, we assessed the frequency of circulating T follicular helper (Tfh) cells in whole blood. IL-21 and IL-17 production was also measured in peripheral blood mononuclear cells (PBMCs) from a subset of 46 of the 62 donors immunophenotyped for Tfh. Results We found a 21.9% (95% CI 5.8, 40.2; p = 3.9 × 10−3) higher frequency of IL-21+ CD45RA− memory CD4+ Teffs in patients with type 1 diabetes (geometric mean 5.92% [95% CI 5.44, 6.44]) compared with healthy donors (geometric mean 4.88% [95% CI 4.33, 5.50]). Consistent with this finding, we found a 14.9% increase in circulating Tfh cells in the patients (95% CI 2.9, 26.9; p = 0.016). Conclusions/interpretation These results indicate that increased IL-21 production is likely to be an aetiological factor in the pathogenesis of type 1 diabetes that could be considered as a potential therapeutic target. Electronic supplementary material The online version of this article (doi:10.1007/s00125-015-3509-8) contains peer-reviewed but unedited supplementary material, which is available to authorised users.
Databáze: OpenAIRE
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