Modulation of immune cell functions by the E3 ligase CBL-b

Modulation of immune cell functions by the E3 ligase CBL-b

Blog Article

Maintenance of immunological tolerance is a critical hallmark of the immune system.Several signaling checkpoints necessary to balance activating and inhibitory input to Vacuum Cleaners immune cells have been described so far, among which the E3 ligase Cbl-b appears to be a central player.Cbl-b is expressed in all leukocyte subsets and regulates several signaling pathways in T cells, NK cells, B cells and different types of myeloid cells.In most cases Cbl-b negatively regulates activation signals through antigen or pattern recognition receptors and co-stimulatory molecules.In line with this function, cblb-deficient immune cells display lower activation thresholds and cblb knockout mice spontaneously develop autoimmunity and are highly susceptible to experimental autoimmunity.

Interestingly, genetic association studies link cblb-polymorphisms with autoimmunity also in humans.Vice versa, the increased activation potential of cblb-deficient cells renders them more potent to fight against malignancies or infections.Accordingly, several reports have shown that cblb knockout mice reject tumors, which mainly depends on cytotoxic T and NK cells.Thus targeting Cbl-b may Vertex Shocks be an interesting strategy to enhance anti-cancer immunity.In this review we summarize the findings on the molecular function of Cbl-b in different cell types and illustrate the potential of Cbl-b as target for immunomodulatory therapies.