دورية أكاديمية

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

التفاصيل البيبلوغرافية
العنوان: IL-21 production by CD4+ effector T cells and frequency of circulating follicular helper T cells are increased in type 1 diabetes patients.
المؤلفون: 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
بيانات النشر: Springer Verlag
//dx.doi.org/10.1007/s00125-015-3509-8
Diabetologia
سنة النشر: 2015
المجموعة: Apollo - University of Cambridge Repository
مصطلحات موضوعية: Adolescent, Adult, Biomarkers, Case-Control Studies, Cells, Cultured, Child, Diabetes Mellitus, Type 1, Female, Humans, Immunologic Memory, Immunophenotyping, Interferon-gamma, Interleukin-17, Interleukins, Lymphocyte Count, Male, Middle Aged, T-Lymphocytes, Helper-Inducer, Up-Regulation, Young Adult
الوصف: 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. ; This work was supported by the JDRF UK Centre for Diabetes - Genes, Autoimmunity and Prevention (D-GAP; 4-2007-1003) in collaboration with M. Peakman and T. Tree at King’s College London, the JDRF, the Wellcome Trust (WT; WT061858/091157 and 083650/Z/07/Z) and the National Institute for Health Research Cambridge Biomedical Research Centre (CBRC). The Cambridge Institute for Medical Research (CIMR) is in receipt of a Wellcome Trust Strategic ...
نوع الوثيقة: article in journal/newspaper
وصف الملف: application/pdf
اللغة: English
العلاقة: https://www.repository.cam.ac.uk/handle/1810/247400Test
الإتاحة: https://www.repository.cam.ac.uk/handle/1810/247400Test
حقوق: Attribution 2.0 UK: England & Wales ; http://creativecommons.org/licenses/by/2.0/ukTest/
رقم الانضمام: edsbas.7F3B5C69
قاعدة البيانات: BASE