Differentiation of functional dendritic cells (DCs) critically depends on the microenvironment. DCs differentiate in hypoxic tumor sites and inflamed or damaged tissue. Because local concentrations of adenosine reach high physiologically relevant levels in these conditions, we assessed the expression of adenosine receptors and the effect of their activation on differentiation of human monocytes...

Tissue effector cells of the monocyte lineage can differentiate into different cell types with specific cell function depending on their environment. The phenotype, developmental requirements, and functional mechanisms of immune protective macrophages that mediate the induction of transplantation tolerance remain elusive. Here, we demonstrate that costimulatory blockade favored accumulation of ...

PURPOSE The purpose of the study was to investigate signaling molecules involved in the acquisition of tolerogenic properties by dendritic cells (DC) in ret transgenic mice with spontaneous melanoma progression and to target these molecules to overcome the barrier for effective melanoma immunotherapy. EXPERIMENTAL DESIGN DC functions and expression patterns of p38 mitogen-activated protein ki...

Persistent colonization with the gastric bacterial pathogen Helicobacter pylori causes gastritis and predisposes infected individuals to gastric cancer. Conversely, it is also linked to protection from allergic, chronic inflammatory, and autoimmune diseases. We demonstrate here that H. pylori inhibits LPS-induced maturation of DCs and reprograms DCs toward a tolerance-promoting phenotype. Our r...

Dendritic cells (DCs) include a heterogeneous family of professional APCs involved in initiation of immunity and in immunologic tolerance. Specifically, peripheral tolerance can be achieved and maintained by promoting regulatory T-cell (Treg) responses and/or T-cell anergy or deletion. Until recently, immature developmental stages of DC differentiation were believed to induce T-cell anergy or T...

While only a small percentage of the liver as dendritic cells, they play a major role in the regulation of liver immunity. Four major types of dendritic cell subsets include myeloid CD8alpha(-)B220(-), lymphoid CD8alpha(+)B220(-), plasmacytoid CD8alpha(-)B220(+), and natural killer dendritic cell with CD8alpha(-)B220(-)NK1.1(+) phenotype. Although these subsets have slightly different character...

Dendritic cells (DC) play a critical role in maintaining immune tolerance to self-antigens and have become a promising immunotherapeutic tool for treating autoimmune diseases such as rheumatoid arthritis (RA). Tolerogenic DC (tolDC) with stable immunosuppressive function can be generated in the laboratory. These modified tolDC induce antigen-specific T cell tolerance in vitro and in vivo, and c...

Lung dendritic cells (DC) play a fundamental role in sensing invading pathogens, as well as in the control of tolerogenic responses in the respiratory tract. Their strategic localization at the site of pathogen entry makes them particularly susceptible to initial viral invasion. Human respiratory syncytial virus (hRSV) and human metapneumovirus (hMPV) belong to the Paramyxoviridae family, withi...

Allograft inflammatory factor-1 (AIF1) is a cytoplasmic scaffold protein shown to influence immune responses in macrophages and microglial cells. The protein contains Ca2+ binding EF-hand and PDZ interaction domains important for mediating intracellular signaling complexes. This study now reports that AIF1 is expressed in CD11c+ dendritic cells (DC) and silencing of expression restrains inducti...

Beta-catenin signaling has recently been tied to the emergence of tolerogenic dendritic cells (DCs). In this article, we demonstrate a novel role for beta-catenin in directing DC subset development through IFN regulatory factor 8 (IRF8) activation. We found that splenic DC precursors express beta-catenin, and DCs from mice with CD11c-specific constitutive beta-catenin activation upregulated IRF...