Our data indicate that allelic variation in or near the coding regions of the FOXP3 gene does not have a major role in the inherited susceptibility to the common form of type 1 diabetes.
Our results indicated an association between FOXP3 and T1D (global p=0.004) and a possible interaction between FOXP3 and the HLA-DR3-DQ2 susceptibility haplotype.
These investigations suggest that altered peripheral blood frequencies of Tregs, as defined by the expression of FOXP3, are not specifically associated with type 1 diabetes and continue to highlight age as an important variable in analysis of immune regulation.
While some progress has been made towards these goals, additional investigations are needed to address the aforementioned knowledge voids including the role for regulatory T cells (Treg), defined by their co-expression of CD4 and CD25 as well as the transcription factor FOXP3, in the pathogenesis and natural history of type 1 diabetes.
These include certain alleles of the cytotoxic T lymphocyte-associated antigen-4 gene (possibly a nonspecific exacerbating molecule of disease risk in several autoimmune diseases), the lymphoid protein tyrosine phosphatase nonreceptor type 22 gene (associated with type 1 diabetes and other autoimmune diseases), TNF-alpha (involved in chronic inflammation, autoimmunity and malignancies) and the FOXP3 gene (expressed by CD4+C25+ regulatory T cells), whose mutations can cause immune dysregulation, polyendocrinopathy and X-linked inheritance syndromes of systemic autoimmunity.
A recent study showed that the presence of the (GT) n microsatellite polymorphism in the FOXP3 gene was associated with enhancer activity, resulting in an effect on type I diabetes mellitus.
Our data showed that the (GT)n microsatelloite polymorphism in the FOXP3/Scrufin gene was associated with Japanese adult onset type 1 diabetes, especially in females, and slowly progressive type 1 diabetes.
In conclusion, children with only T1D generally showed a lower FOXP3 mRNA expression than did children with CD, or with T1D in combination with CD, which suggests impaired regulation of the immune system in children with T1D.
Analysis of positional candidate genes strongly supported CTLA-4 as the gene on 2q associated with APS3v and FOXP3 as the gene on Xp associated with T1D or AITD and APS3v.
Here, 257 single-nucleotide polymorphisms (SNPs) have been genotyped in 19 candidate genes (INS, PTPN22, IL2RA, CTLA4, IFIH1, SUMO4, VDR, PAX4, OAS1, IRS1, IL4, IL4R, IL13, IL12B, CEACAM21, CAPSL, Q7Z4c4(5Q), FOXP3, EFHB) in 2300 affected sib-pair families and tested for association with T1D as part of the Type I Diabetes Genetics Consortium's candidate gene study.
Administration of these cytokines offers an appealing approach to manipulate the Foxp3(+)Treg pool and treat T cell-mediated autoimmunity such as type 1 diabetes.
The frequency of Tregs in peripheral blood was comparable but the FOXP3(+)IFN-γ(+) fraction was significantly increased in patients with type 1 diabetes compared to healthy controls.
Here, we describe a strongly agonistic insulin mimetope that effectively converts naive T cells into Foxp3(+) regulatory T cells in vivo, thereby completely preventing T1D in NOD mice.