Autoantibodies to insulin (IAA), GAD (GADA), insulinoma-associated antigen-2 (IA-2A) and zinc transporter 8 (ZnT8A) were measured in follow-up sera, and genotyping for type 1 diabetes susceptibility genes (HLA-DR/HLA-DQ, INS variable number of tandem repeats [VNTR] and single nucleotide polymorphisms at PTPN22, PTPN2, ERBB3, IL2, SH2B3, CTLA4, IFIH1, KIAA0350 [also known as CLEC16A], CD25, IL18RAP, IL10, COBL) was performed on the DNA samples of children born to a parent with type 1 diabetes and prospectively followed from birth for up to 22 years.
Interrogation of pathways from eight pathway databases yields strong support for enriched pathways, indicating links between Crohn's disease (CD) and cytokine-driven networks that modulate immune responses; between rheumatoid arthritis (RA) and "Measles" pathway genes involved in immune responses triggered by measles infection; and between type 1 diabetes (T1D) and IL2-mediated signaling genes.
Our aim was to evaluate the association of the four IL2 polymorphisms (rs6822844, rs6534349, rs2069762 and rs3136534) with type 1 diabetes (T1D) in the Polish population, and to correlate them with the serum interleukin-2 levels.
A total of 76 T1D patients and 162 controls from Southern Tunisia were recruited for a case-control association study investigating the relationship between sixteen SNPs of the BANK1, IL15 and IL2/IL21 gene region and T1D.
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 β (TGF-β).
The IL2-IL21 association we have identified, if confirmed, suggests a novel role for B cells in T1D pathogenesis through the production of IL-10, and reinforces the importance of IL-10 production by autoreactive CD4(+) T cells.
Here, we have examined IL-2 sensitivity in CD4+ T-cell subsets in 70 individuals with long-standing T1D, allowing us to investigate the effect of low IL-2 sensitivity on Treg frequency and function.
Regulation of IL-2 expression and sensitivity are affected with possible consequences for disease course and severity at long-term type-1-diabetes stages.
In this review article, we focus on the most recent applications of nuclear medicine techniques (mainly <sup>99m</sup>Tc/<sup>111</sup>In white blood cells (WBC) scan, [<sup>18</sup>F]-FDG-PET/CT, [<sup>18</sup>F]-FDG-PET/MRI, and <sup>99m</sup>Tc-IL-2 scintigraphy) in the study of children affected by peripheral bone osteomyelitis, fungal infections, inflammatory bowel diseases, and type 1 diabetes, owing to recent important published evidences of their role in the management of these diseases.
Combination therapies aimed at suppressing effector T cells while using IL-2 to expand Tregs could be beneficial and have been trialed in T1D patients.
A progressive waning in Foxp3<sup>+</sup> regulatory T (T<sub>reg</sub>) cell function provokes autoimmunity in the non-obese diabetic (NOD) mouse model of type 1 diabetes (T1D), a cellular defect rescued by prophylactic IL-2 therapy.
The contribution of polymorphisms in the gene encoding the IL-2 receptor α subunit (<i>IL2RA</i>), which are associated with type 1 diabetes, is difficult to determine because autoimmunity depends on variations in multiple genes, where the contribution of any one gene product is small.
We quantified selected circulating immunological markers in mid-pregnancy (interleukin [IL]-1β, IL-1ra, IL-2Rα, IL-2, -4, -5, -6, -10, -12p70, 13, -17A, GM-CSF, IFN-γ, CXCL10, CCL 2, CCL3, CCL4, TNF) and cord blood plasma (neopterin and kynurenine/tryptophan ratio) in a case-control study with 175 mother/child T1D cases (median age 5.8, range 0.7-13.0 years) and 552 controls.
Since the successful clinical trials of IL-2 to treat patients with autoimmune diseases and inflammatory conditions, including Systemic lupus erythematosus (SLE) and Type 1 Diabetes (T1D), ld IL-2 therapy is a promising strategy to treat autoimmune diseases.
In this study, we measured 12 soluble receptors and ligands from TNF-α/IL6/IL2 pathways in T1D patients with MA (<i>n</i> = 89) and T1D patients without MA (<i>n</i> = 483) participating in the PAGODA study.
Increased T1D disease risk from IL-2 pathway loci in the TwinsUK cohort of human subjects resulted in some similar microbiota changes to those observed in the NOD mouse.
This reduction in UBASH3A, as a consequence of the minor allele at rs1893592, resulted in increased secretion of IL-2, a key cytokine that is required for T-cell activation and function but is deficient in some T1D subjects.
When complexed with human IL-2, F5111.2 induced remission of type 1 diabetes in the NOD mouse model, reduced disease severity in a model of experimental autoimmune encephalomyelitis and protected mice against xenogeneic graft-versus-host disease.
While IL-2 targets anti-tumor cytotoxic lymphocytes (CTLs) for the treatment of patients with melanoma or renal cell carcinoma, IL-2 directed at regulatory T (Treg) cells could have potential therapeutic value in several immune-related diseases including chronic graft-versus-host disease (cGVHD), type 1 diabetes (T1D) and systemic lupus erythematosus (SLE).
Aside from these two approaches, studies and trials have also been conducted on regulatory T cells, dendritic cells, interleukin 2, interleukin 4, M2 macrophages, and rapamycin/interleukin 2 combination therapy to test their effects on patients with T1D.
Whereas, γ<sub>c</sub> expression was positively correlated with IL-2Rα in memory T-cells from healthy controls, no dependency was found for patients with T1D.