Analysis of the expression of candidate genes for type 1 diabetes susceptibility in T cells.
Endocr J
; 61(6): 577-88, 2014.
Article
in En
| MEDLINE
| ID: mdl-24705559
ABSTRACT
Type 1 diabetes is characterized by T-cell-mediated autoimmune destruction of pancreatic ß-cells. Currently, approximately 50 type 1 diabetes susceptibility genes or chromosomal regions have been identified. However, the functions of type 1 diabetes susceptibility genes in T cells are elusive. In this study, we evaluated the correlation between type 1 diabetes susceptibility genes and T-cell signaling. The expression levels of 22 candidate type 1 diabetes susceptibility genes in T cells from nonobese diabetic (NOD), control C57BL/6 (B6), and NOD-control F1 hybrid mice were analyzed in response to 2 key immunoregulatory cytokines interleukin-2 (IL-2) and transforming growth factor ß (TGF-ß). Exogenous gene expression studies were also performed in EL4 and Jurkat E6.1 T-cell lines. Significant differences in the expression of Clec16a, Dlk1, Il2, Ptpn22, Rnls, and Zac1 (also known as Plagl1) were observed in T cells derived from the 3 strains of mice, and TGF-ß differentially influenced the expression of Ctla4, Foxp3, Il2, Ptpn22, Sh2b3, and Zac1. We found that TGF-ß induced Zac1 expression in both primary T cells and EL4 cells and that exogenous expression of Zac1 and ZAC1 in T-cell lines altered the expression of Il2 and DLK1, respectively. The results of our study indicate the possibility that additional genetic pathways underlying type 1 diabetes susceptibility, including those involving Clec16a, Dlk1, Rnls, Sh2b3, and Zac1 under IL-2 and TGF-ß signaling in T cells, may be shared between human and NOD mice.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
T-Lymphocytes
/
Genetic Predisposition to Disease
/
Diabetes Mellitus, Experimental
/
Diabetes Mellitus, Type 1
/
Genetic Association Studies
Type of study:
Prognostic_studies
Limits:
Animals
/
Female
/
Humans
/
Male
Language:
En
Journal:
Endocr J
Journal subject:
ENDOCRINOLOGIA
Year:
2014
Document type:
Article
Affiliation country:
Japan