Pancreatic diabetes mouse models have been developed with cerulein-induced pancreatitis. In these models, longer induction periods than what we employed in the current study were used, and a second insult was necessary to observe endocrine dysfunction. These indicate both dose- and timedependence of the disease extent and the minor direct effect of cerulein on the pancreatic endocrine cells. These aspects of BMP’s complex role in glucose metabolism during pancreatitis deserve further investigation. BMPs and TGF-b belong to a same superfamily and play important roles in the regulation of cellular functions. They share a similar ligand structure and a similar Nilotinib 641571-10-0 downstream signaling cascade. Therefore, they might coordinately modulate organ fibrosis. Themis was identified as a novel mandatory factor for positive selection by five independent groups in 2009. We identified Themis from a set of uncharacterized genes whose expression was restricted to the thymus. Themis knockout mice exhibited significantly reduced numbers of CD4SP and CD8SP T cells both in the thymus and periphery. Inhibitory effects of Themis deficiency on negative selection and T cell activation were controversial among the reports, nevertheless, they were much slighter than that for positive selection. Thus, Themis is a unique molecule that is essential for positive selection, but not for negative selection. Expression of Themis was significantly lower in regulatory T cells compared to conventional T cells, however, study of a natural mutant rat revealed the importance of Themis on the function of Tregs. Since Themis-deficient mice did not exhibit inflammatory bowel disease or autoimmune diseases observed in Tregdeficient mice, functional requirements for Themis in Tregs could be different between rat and mouse. Themis is constitutively associated with Grb2 and is tyrosinephosphorylated by Lck and ZAP-70 upon TCR stimulation. Some groups reported constitutive association of Themis with Vav1, Itk, and PLC-c1. Furthermore, we and other groups demonstrated association of Themis with PLC-c1, LAT, and SLP76 upon TCR-stimulation, indicating that Themis would be a component of the SLP76-LAT signalosome. From these results, Themis is likely to be involved in TCR-mediated signal transduction. Accordingly, TCR-dependent activation of ERK and NFAT, as well as production of IL-2 was significantly reduced in Themis knockdown Jurkat cells. In the Themis-knockout mice, however, results were different. We and other groups observed unaltered activation of ERK and calcium influx in Themis deficient immature DP thymocyte upon anti-CD3 antibody stimulation, although one group reported impaired activation of these signaling events. Moreover, recent study showed that TCR-dependent activation of ERK, p38 and Vav1 were reduced in Themis deficient CD4SP and CD8SP thymocytes.