Dendritic cells (DCs) are potent antigen-presenting cells with a pivotal role in antigen-specific immune responses. Here, we found that the helix-loop-helix transcription factor Id2 is up-regulated during DC development in vitro and crucial for the development of distinct DC subsets in vivo. Id2-/- mice lack Langerhans cells (LCs), the cutaneous contingent of DCs, and the splenic CD8alpha+ DC subset is markedly reduced. Mice deficient for transforming growth factor (TGF)-beta also lack LCs, and we demonstrate here that, in DCs, TGF-beta induces Id2 expression. We also show that Id2 represses B cell genes in DCs. These findings reveal a TGF-beta-Id2 signaling pathway in DCs and suggest a mechanism by which Id2 affects the lineage choice of B cell and DC progenitors.

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Dendritic cells (DC) represent key regulators of the immune system, yet their development from hemopoietic precursors is poorly defined. In this study, we describe an in vitro system for amplification of a Flt3+CD11b+ progenitor from mouse bone marrow with specific cytokines. Such progenitor cells develop into both CD11b+ and CD11b− DC, and CD8α+ and CD8α− DC in vivo. Furthermore, with GM-CSF, these progenitors synchronously differentiated into fully functional DC in vitro. This two-step culture system yields homogeneous populations of Flt3+CD11b+ progenitor cells in high numbers and allows monitoring the consecutive steps of DC development in vitro under well-defined conditions. We used phenotypic and functional markers and transcriptional profiling by DNA microarrays to study the Flt3+CD11b+ progenitor and differentiated DC. We report here on an extensive analysis of the surface Ag expression of Flt3+CD11b+ progenitor cells and relate that to surface Ag expression of hemopoietic stem cells. Flt3+CD11b+ progenitors studied exhibit a broad overlap of surface Ags with stem cells and express several stem cell Ags such as Flt3, IL-6R, c-kit/SCF receptor, and CD93/AA4.1, CD133/AC133, and CD49f/integrin α6. Thus, Flt3+CD11b+ progenitors express several stem cell surface Ags and develop into both CD11b+ and CD11b− DC, and CD8α+ and CD8α− DC in vivo, and thus into both of the main conventional DC subtypes.

Dendritic cells (DC) are professional antigen‐presenting cells that possess both migratory properties and potent T cell stimulatory activity, and that allow the uptake of antigenic material inperipheral tissues and its subsequent presentation in the T cell areas of lymphoid organs. Thus motility represents a central property that is required for DC function. Here we report on the expression of the receptor tyrosine kinase c‐met in DC. c‐Met is the high affinity receptor for scatter factor (SF)/hepatocyte growth factor, and ligand‐activated c‐met exhibits mitogenic, morphogenic andmotogenic activity in vivo and in vitro. c‐Met is signaling competent in DC since it is effectively tyrosine phosphorylated in response to SF ligand. It is demonstrated here that ligand‐activated c‐met regulates DC adhesion to the extracellular matrix component laminin but leaves antigen presenting function unaffected. Importantly, in ear sheet explant experiments activationof c‐met by ligand induces emigration of cutaneous DC (Langerhans cell, LC) from skin, but SF is not a chemoattractant factor for DC. Our results suggest an important role of the c‐met/SF system in DC/LC migration.

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BACKGROUNDThe role of the immune system in the pathogenesis of endometriosis remains elusive. It has been shown that patients have an altered peritoneal environment with increased levels of inflammatory cytokines, activated macrophages and reduced clearance of retrogradely transported endometrial fragments. However, it is not known if this unique inflammatory situation is cause or consequence of endometriosis. This study investigates the impact of a pre-existing peritoneal inflammation on endometriosis establishment in a mouse model.METHODSEndometriosis was induced by intraperitoneal injection of enhanced green fluorescent protein (EGFP)-expressing endometrium in mice. In parallel, a peritonitis model was established via intraperitoneal injection of thioglycolate medium (TM). Finally, endometriosis was induced in the inflamed peritoneal cavity and lesion establishment as well as morphological and histological characteristics were analysed.RESULTSInduction of endometriosis in an inflamed peritoneal cavity resulted in fewer lesions and significantly lower sum of lesion surface area per mouse in the TM-treated group. Additionally, a higher amount of non-attached debris could be detected in the peritoneal cavity of TM-treated mice.CONCLUSIONSAn intraperitoneal inflammation decreases endometriosis establishment in this mouse model. Thus, a pre-existing peritoneal inflammation might not be a factor favouring the development of endometriosis.

Background: T cells play a central role in many inflammatory diseases, hence the identification and validation of T cell-specific target genes will increase the understanding of T cell function in pathologic inflammatory situations. RNA interference (RNAi), with its ability to induce specific gene silencing in mammalian cells, represents a powerful technology to investigate and validate the function of pharmaceutical target genes in vitro and in vivo. The aim of the present study was to systematically explore RNAi-mediated gene-silencing of known T cell-specific model signaling molecules in primary murine T cells in vitro and in vivo.

Ad/PEI/RNA transfection is an efficient means for generating RNA-transduced DCs and for stimulating antigen-specific T cell responses. Polyadenylation of RNA enhances CD8(+) T cell responses and is essential for CD4(+) T cell responses.