IL-10 and IL-12 were both positively associated with T1D risk in the model 2 (RC, 1.19, P=0.006 and 1.07, P=0.02, respectively)-these results were borderline significant in model 1, but showed the same direction as the results from model 2.
IL-10 deregulation plays a role in the development of a large number of inflammatory diseases such as neuropathic pain, Parkinson's disease, Alzheimer's disease, osteoarthritis, rheumatoid arthritis, psoriasis, systemic lupus erythematosus, type 1 diabetes, inflammatory bowel disease, and allergy.
A significant increase in the levels of interleukin-4 (IL-4), IL-10, and transforming growth factor-β, and a decrease in the levels of IL-17 and interferon-γ in concordance with the significant increase in the Treg cell ratio in splenic MNCs (P < 0.05) was shown in T1DM mice treated with AD-MSC's exosomes as compared to T1DM untreated mice.
After stimulation, the percentage of resting Tregs was decreased and that of effector/memory Tregs was increased in both healthy controls and T1D patients, but CD39 expression on effector/memory Tregs was still lower and there was no increase in IL-10 secretion in T1D patients.
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.
Because the role of regulatory T cells in the intestinal inflammation is unknown in coeliac disease (CD) and type 1 diabetes (T1D), the expression of forkhead box P3 (FoxP3), CD25, transforming growth factor-beta, interferon (IFN)-gamma, interleukin (IL)-4, IL-8, IL-10, IL-15 and IL-18 was measured by quantitative reverse transcription-polymerase chain reaction in the small intestinal biopsies from paediatric patients with active or potential CD, T1D and control patients.
Children of parents with type 1 diabetes and prospectively followed from birth for the development of islet autoantibodies and diabetes were genotyped for single-nucleotide polymorphisms at 12 type 1 diabetes susceptibility genes (ERBB3, PTPN2, IFIH1, PTPN22, KIAA0350, CD25, CTLA4, SH2B3, IL2, IL18RAP, IL10 and COBL).
Compared to healthy controls, B10 cell percentages in T1D were significantly lower (5.6±3.5% vs. 6.9±3.3%; P <0.05), produced less IL-10 (15.4±4.3% vs. 29.0±4.5%; P <0.001), and lacked regulatory capacity.
Fas ligand drives insulitis in the non-obese diabetic mouse model of type 1 diabetes (T1D) and negatively regulates IL-10-producing (IL-10<sup>pos</sup>) CD5<sup>+</sup> B cells in pancreata.
Following STZ treatment to induce T1D, NLRP3-deficient mice also exhibited an increase in myeloid-derived suppressor cell and mast cell numbers in the PLNs along with a significant increase in IL-6, IL-10, and IL-4 expression in the pancreatic tissue.
Functional genetic polymorphisms of proinflammatory (T-helper-1: IL-2, IL-12 and IFN-gamma), anti-inflammatory (T-helper-2: IL-4, IL-6 and IL-10) and metabolic (IGF-I, VDR and INS) genes were determined in 206 Dutch simplex families with juvenile onset T1D and the results were analysed using the transmission disequilibrium test.
Higher levels of proinflammatory mediators (IL-17C and BD-2) in the absence of similar changes in mediators associated with homeostasis (interleukin 10 and thymic stromal lymphopoietin) were also observed in T1D-derived primary IEC cultures.
However, addition of anti-IL-7Rα antibodies to peptide/alum vaccination unexpectedly increased non-specific IFN-γ, IL-2 and IL-10 cytokine production and did not result in improved prevention of T1D onset.
However, the Treg cells showed a decreased production of anti-inflammatory (IL-10, IL-35, TGF-β) and increased pro-inflammatory (IFN-γ, IL-2, IL-17) cytokines, indicating a phenotypic shift of Treg cells under T1D condition.
In conclusion, IL-10 promoter gene variants may contribute, but to a minor extent, to disease susceptibility in juvenile type 1 diabetes and should not be included in the routine genetic screening of high-risk individuals.