DRAK2 contributes to type 1 diabetes by negatively regulating IL-2 sensitivity to alter regulatory T cell development.

Drak2-deficient (Drak2) mice are resistant to multiple models of autoimmunity yet effectively eliminate pathogens and tumors. Thus, DRAK2 represents a potential target to treat autoimmune diseases. However, the mechanisms by which DRAK2 contributes to autoimmunity, particularly type 1 diabetes (T1D), remain unresolved.

Cytokines regulate cysteine cathepsins during TLR responses.

TLR activation is an important component of innate immunity but also contributes to the severity of inflammatory diseases. Cysteine cathepsins (Cat) B, L and S, which are endosomal and lysosomal proteases, participate in numerous physiological systems and are upregulated during various inflammatory disorders and cancers. Macrophages have the highest cathepsin expression and are major contributors to inflammation and tissue damage during chronic inflammatory diseases.

New assay using fluorogenic substrates and immunofluorescence staining to measure cysteine cathepsin activity in live cell subpopulations.

Background: Cathepsins are endosomal/lysosomal proteases that play important roles in regulating cell physiological processes in cardiovascular, neurological, musculoskeletal, and immunological systems. Pathophysiological processes are often associated with a change in cathepsin expression and activity, leading to the possibility of using cathepsins as disease markers for diagnosis and prognosis.

Methods: We describe a new assay utilizing an argon laser flow cytometer to measure activities of cysteine cathepsins B, L, and S in live cells using cell permeable fluorogenic cresyl violet-conjugated peptides as selective substrates.

The non-nucleoside antiviral, BAY 38-4766, protects against cytomegalovirus (CMV) disease and mortality in immunocompromised guinea pigs.

New antiviral drugs are needed for the treatment of cytomegalovirus (CMV) infections, particularly in immunocompromised patients. These studies evaluated the in vitro and in vivo activity of the non-nucleosidic CMV inhibitor, BAY 38-4766, against guinea pig cytomegalovirus (GPCMV). Plaque reduction assays indicated that BAY 38-4766 was active against GPCMV, with an IC(50) of 0.

Absence of interleukin-3 does not affect the severity of local and systemic anaphylaxis but does enhance eosinophil infiltration in a mouse model of allergic peritonitis.

Interleukin-3 (IL-3), which is derived from T cells and other sources, can promote the differentiation, proliferation, and migration of mast cells, basophils, and eosinophils. However, little is known about the ability of IL-3 to regulate the function of these cells in IgE-dependent and -independent allergic responses in vivo. Therefore, we sought to investigate the extent to which endogenously produced IL-3 can influence mast cell secretory function, the expression of local and systemic anaphylactic responses, and ragweed-induced eosinophilic peritonitis.