jing xue

Previously we reported functional leukocyte immunoglobulin-like receptor A3 (LILRA3) leads to susceptibility and sub-phenotypes of several autoimmune diseases. LILRA3 levels in blood serum and CD14+ monocytes enhanced in systemic lupus erythematosus and resulted in disease severity. However, the mechanism of LILRA3 in the pathogenesis of autoimmunity remains elusive. This study aims to explore the potential impact of LILRA3 on the differentiation, maturation, and function of monocyte-derived DCs (MoDCs). The human monocytic cell line (THP-1) was cultured to derive MoDCs in vitro. We performed plasmid transfection to examine the impact of LILRA3 on monocyte differentiation. Surface markers on MoDCs were measured using FACS. To assess the function of mature MoDCs, IL-12p70, IFN-γ and IL-4 levels were detected after the mixed leucocyte response by enzyme-linked immunosorbent assay. Western blot assay was employed in this study to determine the signaling pathways in MoDCs activation. LILRA3 promotes MoDCs maturation, our results showed significant up-regulation of CD40, CD80, CD86, CD209, and HLA-DR and increased production of pro-inflammatory cytokine IL-12. LILRA3-treated MoDCs exhibited a robust proliferation of allogeneic CD4+ T cells and induced naïve CD4+ T cell polarization into the Th1 phenotype. Furthermore, the preceding activation of MoDCs maturation and LILRA3 function might be attributed to p38 MAPK and STAT1 signaling pathway’s aberrant activation. This is the first study to report that LILRA3 played a critical role in promoting MoDCs maturation and directing MoDCs to modulate Th1 cell differentiation, which may have a role in the pathogenesis of autoimmune diseases.

There are much heterogeneity in the genetic variation of type 2 diabetes (T2D).The purpose of this study was to investigate the association of seven novel genetic loci identified in a recent genome-wide association studies (GWAS) with T2D in Chinese Dong populations. A case-controlled study was performed in individuals of Chinese Dong nationality. The genotypes of PARD3B (rs849230), LOC729993 (rs149228), EPHA4 (rs16862811), HNT (rs3099797), PTPRD (rs17584499 and rs649891), TOMM7 (rs2240727) genes were determined using Multiplex PCR-SNaPshot. The independent association between each polymorphism and T2D was assessed using unconditional binary logistic regression analysis (BLR). A total of 136 cases of T2D and 136 control subjects were enrolled in the study. The polymorphism of rs2240727 in TOMM7 gene was associated with T2D (odds ratio (OR) = 1.65, per copy of the risk T allele, P = 0.004). In addition, CT and TT were risk genotypes for T2D (OR (95% CIs):2.64 (1.28-5.45) and 3.42 (1.58-7.41) respectively). After correcting for multiple testing, the above results remained significant (all P < 0.05). After adjusting for the confounders of age, gender, and BMI, the association between T2D and rs2240727 remained significant (P < 0.01). There were significantly statistical difference in levels of fasting plasm glucose(FPG) among genotypes of rs2240727 in controls and patients, the levels of FPG were significantly higher in CT and TT genotypes than in CC genotype in both groups(all P < 0.05). The rs2240727 genetic variant in TOMM7 was associated with T2D of Chinese Dong individuals, and might enhance the risk of T2D by affecting the level of FPG.