Showing papers on "CBLB published in 2014"
TL;DR: It is reported that the loss of Cbl-b facilitates T helper 2 (Th2) and Th9 cell differentiation in vitro and introduces Stat6 deficiency into Cblb−/− mice abrogates hyper-Th2 responses but only partially attenuates Th9 responses.
62 citations
TL;DR: It is shown that CBL-B expression is reduced in CD4+ T cells from relapsing-remitting MS (RR-MS) patients during relapse and a role of the CBLB rs12487066 variant in the interactions of a genetic risk factor and IFN function during viral infections in MS is suggested.
Abstract: Multiple sclerosis (MS) is an autoimmune disease of the CNS, and autoreactive CD4(+) T cells are considered important for its pathogenesis. The etiology of MS involves a complex genetic trait and environmental triggers that include viral infections, particularly the EBV. Among the risk alleles that have repeatedly been identified by genome-wide association studies, three are located near the Casitas B-lineage lymphoma proto-oncogene b gene (CBLB). The CBLB protein (CBL-B) is a key regulator of peripheral immune tolerance by limiting T cell activation and expansion and hence T cell-mediated autoimmunity through its ubiquitin E3-ligase activity. In this study, we show that CBL-B expression is reduced in CD4(+) T cells from relapsing-remitting MS (RR-MS) patients during relapse. The MS risk-related single nucleotide polymorphism of CBLB rs12487066 is associated with diminished CBL-B expression levels and alters the effects of type I IFNs on human CD4(+) T cell proliferation. Mechanistically, the CBLB rs12487066 risk allele mediates increased binding of the transcription factor C/EBPβ and reduced CBL-B expression in human CD4(+) T cells. Our data suggest a role of the CBLB rs12487066 variant in the interactions of a genetic risk factor and IFN function during viral infections in MS.
32 citations
TL;DR: The results here show that in response to a regimen of high fat or high glucose diets, Mstn levels were induced in muscle and liver of mice, and molecular analysis suggested that the increased MStn levels resulted in increased expression of Cblb in a Smad3-dependent manner, which strongly suggest that increased glucose levels and high fat diet, both, result in increased circulatory MSTn levels.