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Title:
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B-Lymphocyte Phenotype Determines T-Lymphocyte Subset Differentiation in Autoimmune Diabetes
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Author:
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Egia-Mendikute, Leire; Arpa i Puigdemont, Berta; Rosell Mases, Estela; Corral-Pujol, Marta; Carrascal, Jorge; Carrillo, Jorge; Mora Giral, Concepció; Chapman, Harold; Panosa, Anaïs; Vives Pi, Marta; Stratmann, Thomas; Serreze, David; Verdaguer Autonell, Joan
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Notes:
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Previous studies indicate that B-lymphocytes play a key role activating diabetogenic T-lymphocytes during the development of autoimmune diabetes. Recently, two transgenic NOD mouse models were generated: the NOD-PerIg and the 116C-NOD mice. In NOD-PerIg mice, B-lymphocytes acquire an activated proliferative phenotype and support accelerated autoimmune diabetes development. In contrast, in 116C-NOD mice, B-lymphocytes display an anergic-like phenotype delaying autoimmune diabetes onset and decreasing disease incidence. The present study further evaluates the T- and B-lymphocyte phenotype in both models. In islet-infiltrating B-lymphocytes (IIBLs) from 116C-NOD mice, the expression of H2-Kd and H2-Ag7 is decreased, whereas that of BAFF, BAFF-R, and TACI is increased. In contrast, IIBLs from NOD-PerIg show an increase in CD86 and FAS expression. In addition, islet-infiltrating T-lymphocytes (IITLs) from NOD-PerIg mice exhibit an increase in PD-1 expression. Moreover, proliferation assays indicate a high capacity of B-lymphocytes from NOD-PerIg mice to secrete high amounts of cytokines and induce T-lymphocyte activation compared to 116C B-lymphocytes. This functional variability between 116C and PerIg B-lymphocytes ultimately results in differences in the ability to shape T-lymphocyte phenotype. These results support the role of B-lymphocytes as key regulators of T-lymphocytes in autoimmune diabetes and provide essential information on the phenotypic characteristics of the T- and B-lymphocytes involved in the autoimmune response in autoimmune diabetes.
The research described in this publication was partially supported by the Plan Nacional de I+D+i of the Spanish Ministry of Science and Innovation (SAF2016-77227-R), CIBER of Diabetes and Associated Metabolic Diseases (CIBERDEM) that is an initiative from Instituto de Salud Carlos III (Spain) and the Juvenile Diabetes Research Foundation 5-2005-1133 innovative research grant. LE-M, ER-M, and MC-P, were supported by pre-doctoral fellowships from the University of Lleida and the IRBLleida. JCarrascal was supported by a FPI pre-doctoral fellowship (BES-2007-15221) from the Spanish Ministry of Science and Innovation. JV, MC-P, and TS are associate professors from the Serra-Hunter Program from the Catalan Government. DS is supported by NIH grants DK46266 and DK95735 as well as by grants from the Juvenile Diabetes Research Foundation, the American Diabetes Association, and Helmsley Charitable Trust (#2014PG-T1D048). We thank Dr. Jeremy Racine and Mr. Qiming Wang for reviewing the manuscript. Special thanks to Ms. D. Cullell-Young for English grammar assistance. |
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Subject(s):
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-Type 1 diabetes
-NOD mouse
-Transgenic mouse model
-B-lymphocyte phernotype
-T-lymphocyte phernotype |
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Rights:
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cc-by (c) Egia Mendikute et al., 2019
http://creativecommons.org/licenses/by/4.0/
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Document type:
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Article
Article - Published version |
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Published by:
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Frontiers Media
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