Project description:Analyze the effect of TLR9 deficiency on immue cell function at the gene expression level. Our hypothesis was that TLR9 deficiency promotes CD73 expression in T cells thus regulates autoimmune diabetes development in NOD mice. Sorted TCRb+ cells were pooled from several mice for furhter RNA extraction and cRNA labeling.
Project description:Analyze the effect of TLR9 deficiency on immue cell function at the gene expression level. Our hypothesis was that TLR9 deficiency promotes CD73 expression in T cells thus regulates autoimmune diabetes development in NOD mice.
Project description:Appropriate tuning of protein homeostasis through mobilization of the unfolded protein response (UPR) is key to the capacity of pancreatic beta cells to cope with highly variable demand for insulin synthesis. An efficient UPR ensures a sufficient beta cell mass and secretory output but can also affect beta cell resilience to autoimmune aggression. However, the factors regulating protein homeostasis in the face of metabolic and immune challenges are insufficie tly understood. We examined beta cell adaptation to stress in mice deficient for insulin-degrading enzyme (IDE), a ubiquitous protease with high affinity for insulin, a putative ill-defined role in protein homeostasis, and genetic association with type 2 diabetes. IDE deficiency induces a low-level UPR in both standard and autoimmune non-obese diabetic (NOD) mice, associated with rapamycin-sensitive beta cell proliferation, as well as protection from diabetes in NOD mice. Moreover, in NOD islets, IDE deficiency specifically induces strong upregulation of regenerating islet-derived protein 2, a protein attenuating inflammation and protecting from autoimmunity. Our findings establish a role of IDE in islet cell protein homeostasis, corroborate the link between low-level UPR and proliferation, and identify an anti-inflammatory islet cell response uncovered in the absence of IDE of potential interest in autoimmune diabetes.
Project description:Transgenic overexpression of Nfkbid in NOD mice causes robust type 1 diabetes protection associated with expansion of Tregs with increased suppressive capacity. Complementarily, Nfkbid ablation leads to decreased Treg numbers, decreased suppressive capacity and accelerated diabetes.The goal of this experiment was to further identify molecular mechanisms underlying strong protection and susceptibility from type 1 diabetes imbued by modifying Nfkbid expression. mRNA sequencing analysis of Tregs from NOD mice with absent or overexpressed Nfkbid was performed. Differential gene expression was calculated and Ingenuity Pathway analyses showed enrichment of cellular replication pathways. Understanding the mechanisms underlying protection from Nfkbid overexpression may lead to novel therapeutic avenues.
Project description:We collected whole genome testis expression data from hybrid zone mice. We integrated GWAS mapping of testis expression traits and low testis weight to gain insight into the genetic basis of hybrid male sterility.
