Qiaohong Lai

MBD2 regulates TH17 differentiation and experimental autoimmune encephalomyelitis by controlling the homeostasis of T-bet/Hlx axis.

Unlike genetic alterations, epigenetic modifications are reversible and amenable to pharmacological interventions, which make them appealing targets for clinical therapy. However, little is known about epigenetic regulation in experimental autoimmune encephalomyelitis (EAE). Here we demonstrated that methyl-CpG-binding domain protein 2 (MBD2), an epigenetic regulator, controls autoimmunity and EAE through T-bet/Hlx. Tbx21 and Hlx underwent a DNA methylation turnover upon polarizations and a unique methylation pattern was essential for TH17 development. Loss of Mbd2 resulted in a defect for reading the information encoded by this methylation turnover, which disrupted the homeostasis of T-bet/Hlx axis and suppressed TH17 differentiation. DNA demethylation induced similar effect on helper T cell differentiation. Therefore, Mbd2(-/-) mice were completely protected from EAE. Pathogenic splenocytes isolated from wild-type mice challenged with MOG35-55 could adoptively transfer disease to Mbd2(-/-) mice. In addition, Mbd2(-/-) mice reconstituted with unstimulated wild-type splenocytes developed EAE as wild-type mice did. These data would provide novel insights into epigenetic regulation of EAE.

Assessment of type 2 diabetes risk conferred by SNPs rs2241766 and rs1501299 in the ADIPOQ gene, a case/control study combined with meta-analyses

We conducted a case/control study to assess the impact of two SNPs, rs2241766 and rs1501299 within the ADIPOQ gene, on type 2 diabetes (T2D) susceptibility in a Chinese Han dataset (741 cases and 902 controls). SNP rs2241766 was found significantly associated with T2D risk in the additive model, dominant model and recessive model. A marginal association was detected for SNP rs1501299 in the additive model and recessive model after Bonferroni correction, and haplotype analysis provided additional evidence supporting the association between these two SNPs and T2D risk. A meta-analysis including 29 published datasets along with current dataset was next carried out to further confirm the association. In consistent with our case/control results, rs2241766 showed a significant association with T2D in the dominant model and additive model, and the association between rs1501299 and T2D was also characterized in the homozygote model, dominant model, recessive model, and additive model. Of note, the association became much stronger in East Asians after exclusion of ethnic stratification. Together, our data support that the rs2241766 and rs1501299 polymorphisms within the ADIPOQ gene confer genetic susceptibility for type 2 diabetes, especially in the Chinese Han population.