Mice deficient for paired immunoglobulin (Ig)-like receptor B (PIR-B) show defective regulation of receptor-mediated activation in antigen-presenting cells. Older PIR-B(-/-) mice had an increased number of peritoneal B1 cells. Splenic PIR-B(-/-) B2 cells were constitutively activated and proliferated much more than those from wild-type mice upon B cell receptor ligation. T helper type 2 (T(H)2)-prone humoral responses were augmented in PIR-B(-/-) mice upon immunization with T-dependent antigens, including increased interleukin 4 and decreased interferon-gamma responses, as well as enhanced IgG1 and IgE production. Impaired maturation of dendritic cells (DCs), possibly due to perturbed intracellular signaling, was responsible for the skewed responses. Thus, PIR-B is critical for B cell suppression, DC maturation and for balancing T(H)1 and T(H)2 immune responses.
Dendritic cells (DCs) loaded with tumor-associated Ags (TAAs) act as potent adjuvant that initiates antitumor immune responses in vivo. However, TAA-based DC vaccination requires prior identification of TAAs. Apoptotic tumor cells (ATCs) can be an excellent source for DC loading because their potential uncharacterized Ags would be efficiently presented to T cells without any prior characterization and isolation of these Ags. However, ATCs alone are considered to be inefficient for activating antitumor immunity, possibly because of their inability to induce DC maturation. In this study, the aim was to enhance antitumor immune response by taking advantage of ATCs that have been opsonized with IgG (ATC-immune complexes, ATC-ICs) so as to target them to FcR for IgG (FcγRs) on DCs. It was found that when compared with ATCs, ATC-ICs were efficiently internalized by DCs via FcγRs, and this process induced maturation of DCs, which was more efficient than that of ATCs. Importantly, ATC-IC loading was shown to be more efficient than ATCs alone in its capacity for inducing antitumor immunity in vivo, in terms of cytotoxic T cell induction and tumor rejection. These results show that using ATC-ICs may overcome the limitations and may enhance the immune response of current ATC-based DC vaccination therapy.
hosphorus homeostasis at the organismal level is maintained by balancing phosphate intake and excretion. Specifically, the amount of phosphate excreted into urine is regulated so as to become equal to the amount of phosphate absorbed from the digestive tract. 1 The amount of urinary phosphate excretion is primarily regulated by the endocrine axis consisting of fibroblast growth factor-23 (FGF23) and its obligate coreceptor klotho. FGF23 is a hormone secreted from osteoblasts and osteocytes in response to phosphate intake. FGF23 binds to the binary complex of FGF receptor and klotho expressed in renal tubules and suppresses phosphate reabsorption, thereby promoting urinary
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.