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ABSTRACT: Many patients with asthma or chronic obstructive pulmonary disease receive corticosteroids; thus, prevention and treatment of corticosteroid-induced bone loss is important. Patients taking corticosteroids should maintain a daily calcium [...]

ABSTRACT: Patients with asthma or chronic obstructive pulmonary disease (COPD) may be at increased risk for osteoporosis because of the effects of corticosteroids and other comorbid factors. While excessive use [...]

Regulation of gp130 expression in cultured mouse mast cells and role for IL‐6 trans‐signaling in increasing survival and cytokine production. It is reported that human and mouse mast cells express the IL‐27R, which consists of WSX‐1 (the IL‐27Rα subunit) and the signal‐transducing subunit gp130. Although it has been proposed that IL‐27 may negatively regulate mast cell‐dependent, immediate hypersensitivity responses directly, this has yet to be examined specifically. We found that mouse BMMC and primary peritoneal mast cells are unresponsive to IL‐27. Consistent with this, gp130 protein in resting BMMC was not on the cell surface to a measurable degree but was found intracellularly, and data are consistent with incompletely processed N‐linked glycosylation. Furthermore, BMMC constitutively expressed SOCS3, a major negative regulator of gp130 signaling. However, BMMC stimulation with IL‐10 and consequential STAT3 activation increased gp130 expression, which resulted in a functional gp130 receptor on the BMMC cell surface. IL‐10 has not been previously shown to regulate gp130 expression, which on the BMMC surface, permitted IL‐6 trans‐signaling, found to increase survival under limiting conditions and enhance IL‐13 and TNF‐α secretion. This study identifies factors that regulate mouse mast cell gp130 expression and signaling and makes conspicuous the limitations of using cultured mouse mast cells to study the effects of the IL‐6/IL‐12 cytokine family on mast cell biology.

ABSTRACTChallenge with the intracellular protozoan parasite Toxoplasma gondiiinduces a potent CD8+T-cell response that is required for resistance to infection, but many questions remain about the factors that regulate the presentation of major histocompatibility complex class I (MHC-I)-restricted parasite antigens and about the role of professional and nonprofessional accessory cells. In order to address these issues, transgenic parasites expressing ovalbumin (OVA), reagents that track OVA/MHC-I presentation, and OVA-specific CD8+T cells were exploited to compare the abilities of different infected cell types to stimulate CD8+T cells and to define the factors that contribute to antigen processing. These studies reveal that a variety of infected cell types, including hematopoietic and nonhematopoietic cells, are capable of activating an OVA-specific CD8+T-cell hybridoma, and that this phenomenon is dependent on the transporter associated with antigen processing and requires live T. gondii. Several experimental approaches indicate that T-cell activation is a consequence of direct presentation by infected host cells rather than cross-presentation. Surprisingly, nonprofessional antigen-presenting cells (APCs) were at least as efficient as dendritic cells at activating this MHC-I-restricted response. Studies to assess whether these cells are involved in initiation of the CD8+T-cell response to T. gondiiin vivo show that chimeric mice expressing MHC-I only in nonhematopoietic compartments are able to activate OVA-specific CD8+T cells upon challenge. These findings associate nonprofessional APCs with the initial activation of CD8+T cells during toxoplasmosis.

Patients with primary hypogammaglobulinemia have been reported to have encephalopathy, but progressive multifocal leukoencephalopathy (PML) due to JC virus reactivation is a rare cause.