The immunoreceptor adapter protein DAP12 suppresses B lymphocyte-driven adaptive immune responses

DAP12, an immunoreceptor tyrosine-based activation motif-bearing adapter protein, is involved in innate immunity mediated by natural killer cells and myeloid cells. We show that DAP12-deficient mouse B cells and B cells from a patient with Nasu-Hakola disease, a recessive genetic disorder resulting from loss of DAP12, showed enhanced proliferation after stimulation with anti-IgM or CpG. Myeloid-associated immunoglobulin-like receptor (MAIR) II (Cd300d) is a DAP12-associated immune receptor. Like DAP12-deficient B cells, MAIR-II-deficient B cells were hyperresponsive. Expression of a chimeric receptor composed of the MAIR-II extracellular domain directly coupled to DAP12 into the DAP12-deficient or MAIR-II-deficient B cells suppressed B cell receptor (BCR)-mediated proliferation. The chimeric MAIR-II-DAP12 receptor recruited the SH2 domain-containing protein tyrosine phosphatase 1 (SHP-1) after BCR stimulation. DAP12-deficient mice showed elevated serum antibodies against self-antigens and enhanced humoral immune responses against T cell-dependent and T cell-independent antigens. Thus, DAP12-coupled MAIR-II negatively regulates B cell-mediated adaptive immune responses.     

Oral motor function and masticatory performance in the community-dwelling elderly

This study was performed to ascertain the relationships between oral motor functions, such as those of the tongue and lips, and age in the community-dwelling elderly, as well as to investigate the effects of these factors on masticatory performance. The subjects were 268 healthy elderly Japanese living in Kyoto. They were divided into four age groups and further classified into the following two groups by the presence or absence of posterior occlusal support: Eichner A or B1-B3 (group A), and Eichner B4 or C (group B). They were wearing removable or fixed dentures if they had missing teeth. Oral function evaluation items included (1) masticatory performance and (2) oral motor skills. Significant differences were noted among the age groups in tongue pressure within group A (P < 0.01) and group B (P < 0.05), and in the number of repetitions of the syllables /ta/ and /ka/ in group B (/ta/: P < 0.05, /ka/; P < 0.01). The number of natural teeth (β = 0.463, P < 0.001) in group A and tongue pressure (β = 0.436, P < 0.001) in group B were the only predictors of masticatory performance when the data were analyzed by multiple regression analysis. The tongue may compensate for the missing teeth in masticatory performance of those elderly who have lost their natural teeth. The results of this study highlight the importance of tongue function in masticatory performance.     

Tongue function is important for masticatory performance in the healthy elderly: a cross-sectional survey of community-dwelling elderly

Purpose

The aim of this study was to determine the influences of oral motor function such as tongue function and bite force on masticatory performance in the elderly.

Allergic conversion of protective mucosal immunity against nasal bacteria in patients with chronic rhinosinusitis with nasal polyposis

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Immune Semaphorins: Novel Features of Neural Guidance Molecules

Introduction  The immune and nervous system have various common features in the functional characteristics. Both have an intricate network of synaptic connections and an exquisite communication system that enables intercellular signal transduction. They also share a number of messenger molecules such as cytokines and chemical mediators. Discussion  Semaphorins, well-defined axonal guidance molecules in the nervous system, also play critical roles in immune regulation. Various types of semaphorins, including secreted, transmembrane, truncated, and glycosylphosphatidylinositol-anchored forms, function during immune responses. However, some semaphorins utilize receptors in the immune system that are distinct from receptors in the nervous system. Conclusion  This review presents a current overview of ‘immune semaphorins’ and their receptors, providing insight into the pleiotropic activity of this protein family.     

Effect of bioactive filler content on mechanical properties and osteoconductivity of bioactive bone cement.

We took three types of bioactive bone cement (designated AWC, HAC, and TCPC), each with a different bioactive filler, and evaluated the influence of each filler on the mechanical properties and osteoconductivity of the cement. The cements consisted of bisphenol-a-glycidyl methacrylate-based (Bis-GMA based) monomers as an organic matrix, with a bioactive filler of apatite/wollastonite containing glass-ceramic (AW-GC) or sintered hydroxyapatite (HA) or beta-tricalcium phosphate (beta-TCP) powder. Each filler was mixed with the monomers in proportions of 50, 70, and 80% (w/w), giving a total of nine cement subgroups. The nine subgroups were designated AWC50, AWC70, AWC80, HAC50, HAC70, HAC80, TCPC50, TCPC70, and TCPC80. The compressive and bending strengths of AWC were found to be higher than those of HAC and TCPC for all bioactive filler contents. We also evaluated the cements in vivo by packing them into the intramedullary canals of rat tibiae. To compare the osteoconductivity of the cements, an affinity index was calculated for each cement; it equaled the length of bone in direct apposition to the cement, expressed as a percentage of the total length of the cement surface. Microradiographic examination up to 26 weeks after implantation revealed that AWC showed a higher affinity index than HAC and TCPC for each filler content although the affinity indices of all nine subgroups (especially the AWC and HAC subgroups) increased with time. New bone had formed along the AWC surface within 4 weeks, even in the cement containing AW-GC filler at only 50% (w/w); observation of the cement-bone interfaces using a scanning electron microscope showed that all the cements had directly contacted the bone. At 4 weeks the AWC had bonded to the bone via a 10 micron-thick reactive layer; the width of the layer, in which partly degraded AW-GC particles were seen, became slightly thicker with time. On the other hand, in the HAC- and TCPC-implanted tibiae, some particles on the cement surface were surrounded by new bone and partly absorbed or degraded. The results suggest that the stronger bonding between the inorganic filler and the organic matrix in the AWC cements gave them better mechanical properties. The results also indicate that the higher osteoconductivity of AWC was caused by the higher reactivity of the AW-GC powder on the cement surface.     

Short-circuiting long-lived humoral immunity by the heightened engagement of CD40

Agonistic alpha CD40 Ab's have been shown to be potent immune adjuvants for both cell- and humoral-mediated immunity. While enhancing short-lived humoral immunity, the administration of a CD40 agonist during thymus-dependent immune responses ablates germinal center formation, prematurely terminates the humoral immune response, blocks the generation of B cell memory, and prevents the generation of long-lived bone marrow plasma cells. Interestingly, some of these effects of heightened CD40 engagement could be mimicked by enhancing the magnitude of antigen-specific T cell help. Taken together, these studies demonstrate that as the magnitude of CD40 signaling intensifies, the fate of antigen-reactive B cells can be dramatically altered. These are the first studies to describe the multifaceted function of CD40 in determining the fate of antigen-reactive B cells and provide novel insights into how CD40 agonists can short-circuit humoral immunity.     

The absence of IgE antibody-mediated augmentation of immune responses in CD23-deficient mice.

The CD23 antigen, a low-affinity receptor for IgE (Fc epsilon RII), is a type II membrane-bound glycoprotein expressed on various cells, particularly mature B cells. A number of functions have been ascribed to CD23, including specific regulation of IgE production, IgE-mediated cytotoxicity and release of mediators, IgE-dependent antigen focusing, promotion of B-cell growth, prevention of germinal center B cells from apoptosis, proliferation of myeloid precursors, and maturation of early thymocytes. It is not clear whether these activities represent in vivo functions. To explore in vivo functions of CD23, we have produced CD23-deficient mice. These mice displayed normal lymphocyte differentiation and could mount normal antibody responses, including IgE responses upon immunization with T-dependent antigens and infection with Nippostrongyrus brasiliensis. Germinal center formation after immunization and in vitro proliferative response of B cells were not affected in mutant mice. However, antigen-specific IgE-mediated enhancement of antibody responses was severely impaired.