Generation of Interferon α–Producing Predendritic Cell (Pre-Dc)2 from Human Cd34+ Hematopoietic Stem Cells

Upon viral stimulation, the natural interferon (IFN)-α/β–producing cells (IPCs; also known as pre-dendritic cells (DCs 2) in human blood and peripheral lymphoid tissues rapidly produce huge amounts of IFN-α/β. After performing this innate antiviral immune response, IPCs can differentiate into DCs and strongly stimulate T cell–mediated adaptive immune responses. Using four-color immunofluorescence flow cytometry, we have mapped the developmental pathway of pre-DC2/IPCs from CD34+ hematopoietic stem cells in human fetal liver, bone marrow, and cord blood. At least four developmental stages were identified, including CD34++CD45RA− early progenitor cells, CD34++CD45RA+ late progenitor cells, CD34+CD45RA++CD4+interleukin (IL)-3Rα++ pro-DC2, and CD34−CD45RA++ CD4+IL-3Rα++ pre-DC2/IPCs. Pro-DC2s have already acquired the capacity to produce large amounts of IFN-α/β upon viral stimulation and to differentiate into DCs in culture with IL-3 and CD40 ligand. CD34++CD45RA− early progenitor cells did not have the capacity to produce large amounts of IFN-α/β in response to viral stimulation; however, they can be induced to undergo proliferation and differentiation into IPCs/pre-DC2 in culture with FLT3 ligand

Популяризация материалов о жизни и творчестве А.И. Солженицына в Рязанской областной библиотеке

Public libraries, realizing their social functions, contribute to the social and cultural development of the region. One of their main functions is education, dissemination of knowledge that forms the culture of person and worldview attitudes. The article reveals the long-term activity of the Ryazan regional universal scientific library named after Gorky on the information resources representing the pages of life and work of Alexander Solzhenitsyn, the Nobel Prize laureate in literature, Honorary citizen of Ryazan, the world famous writer and publicist, educator, public and political person. The author reveals the significance of creative work of A.I. Solzhenitsyn in the public life of Ryazan and the region; analyses the experience of library work with the documents from the library holdings. As example, the author presents educational projects implemented in the partnership with organizations and institutions of the city: the Scientific and educational centre for the study of heritage of A.I. Solzhenitsyn, the Ryazan Solzhenitsyn society, as well as with writers and local historians. The article considers classification of types of resources on A.I. Solzhenitsyn, including personal documentary sources of the writer’s life, the documents of book collections of libraries, bibliographic databases, catalogues and card files, electronic resources created by librarians; provides examples of the above resource groups, including electronic ones collected through partner organizations and posted on the website of the Ryazan regional universal scientific library named after Gorky.Общедоступные публичные библиотеки, реализуя социальные функции, содействуют социально-культурному развитию региона. Одна из основных функций — просветительская, представляющая собой распространение знаний, формирующих культуру человека, основы его мировоззрения. В статье раскрыта многолетняя деятельность Рязанской областной универсальной научной библиотеки имени Горького (Рязанской ОУНБ им. Горького) по продвижению информационных ресурсов, представляющих страницы жизни и творчества лауреата Нобелевской премии по литературе, Почетного гражданина г. Рязани, всемирно известного писателя и публициста, просветителя, общественного и политического деятеля Александра Исаевича Солженицына. Раскрыто значение творчества А.И. Солженицына в общественной жизни Рязани и региона; анализируется опыт работы Рязанской ОУНБ им. Горького с документами, содержащимися в библиотечном фонде; в качестве примеров приводятся просветительские проекты, реализуемые в партнерстве с организациями и учреждениями города: Научно-просветительским центром по изучению наследия А.И. Солженицына, Рязанским Солженицынским обществом, писателями и краеведами. В статье рассматривается видовая классификация ресурсов о А.И. Солженицыне, включающая личные документальные источники из жизни писателя, а также документы из книжного фонда библиотек; библиографические базы данных, каталоги и картотеки; электронные ресурсы, созданные библиотекарями. Приводятся примеры ресурсов, в том числе электронных, собранных с помощью организаций-партнеров и размещенных на сайте Рязанской ОУНБ им. Горьког

The Development of Murine Plasmacytoid Dendritic Cell Precursors Is Differentially Regulated by FLT3-ligand and Granulocyte/Macrophage Colony-Stimulating Factor

Plasmacytoid predendritic cells or type 1 interferon (IFN)-producing cells (IPCs) have recently been identified in mice. Although culture systems giving rise to different murine dendritic cell subsets have been established, the developmental regulation of murine plasmacytoid IPCs and the culture conditions leading to their generation remain unknown. Here we show that large numbers of over 40% pure CD11c+CD11b−B220+Gr-1+ IPCs can be generated from mouse bone marrow cultures with FLT3-ligand. By contrast GM-CSF or TNF-α, which promote the generation of CD11c+CD11b+B220− myeloid DCs, block completely the development of IPCs. IPCs generated display similar features to human IPCs, such as the plasmacytoid morphology, the ability to produce large amounts of IFN-α in responses to herpes simplex virus, and the capacity to respond to ligands for Toll-like receptor 9 (TLR-9; CpG ODN 1668), but not to ligands for TLR-4 (lipopolysaccharide [LPS]). Unlike human IPCs which produce little IL-12p70, mouse IPCs produce IL-12p70 in response to CpG ODN 1668 and herpes simplex virus. This study demonstrates that the development of murine CD11c+CD11b−B220+Gr-1+ IPCs and CD11c+CD11b+B220− myeloid DCs is differentially regulated by FLT3-ligand and granulocyte/macrophage colony-stimulating factor. Human IPCs and mouse IPCs display different ability to produce IL-12p70. Large numbers of mouse IPCs can now be obtained from total bone marrow culture

Human Dendritic Cells Activated by TSLP and CD40L Induce Proallergic Cytotoxic T Cells

Human thymic stromal lymphopoietin (TSLP) is a novel epithelial cell–derived cytokine, which induces dendritic cell (DC)-mediated CD4+ T cell responses with a proallergic phenotype. Although the participation of CD8+ T cells in allergic inflammation is well documented, their functional properties as well as the pathways leading to their generation remain poorly understood. Here, we show that TSLP-activated CD11c+ DCs potently activate and expand naive CD8+ T cells, and induce their differentiation into interleukin (IL)-5 and IL-13–producing effectors exhibiting poor cytolytic activity. Additional CD40L triggering of TSLP-activated DCs induced CD8+ T cells with potent cytolytic activity, producing large amounts of interferon (IFN)-γ, while retaining their capacity to produce IL-5 and IL-13. These data further support the role of TSLP as initial trigger of allergic T cell responses and suggest that CD40L-expressing cells may act in combination with TSLP to amplify and sustain pro-allergic responses and cause tissue damage by promoting the generation of IFN-γ–producing cytotoxic effectors

Myeloid DAP12-associating lectin (MDL)-1 regulates synovial inflammation and bone erosion associated with autoimmune arthritis.

DNAX adaptor protein 12 (DAP12) is a trans-membrane adaptor molecule that transduces activating signals in NK and myeloid cells. Absence of functional Dap12 results in osteoclast defects and bone abnormalities. Because DAP12 has no extracelluar binding domains, it must pair with cell surface receptors for signal transduction. There are at least 15 known DAP12-associating cell surface receptors with distinct temporal and cell type-specific expression patterns. Our aim was to determine which receptors may be important in DAP12-associated bone pathologies. Here, we identify myeloid DAP12-associating lectin (MDL)-1 receptor (also known as CLEC5A) as a key regulator of synovial injury and bone erosion during autoimmune joint inflammation. Activation of MDL-1 leads to enhanced recruitment of inflammatory macrophages and neutrophils to the joint and promotes bone erosion. Functional blockade of MDL-1 receptor via Mdl1 deletion or treatment with MDL-1-Ig fusion protein reduces the clinical signs of autoimmune joint inflammation. These findings suggest that MDL-1 receptor may be a therapeutic target for treatment of immune-mediated skeletal disorders

Distinct Cytokine Profiles of Neonatal Natural Killer T Cells after Expansion with Subsets of Dendritic Cells

Natural killer T (NKT) cells are a highly conserved subset of T cells that have been shown to play a critical role in suppressing T helper cell type 1–mediated autoimmune diseases and graft versus host disease in an interleukin (IL)-4–dependent manner. Thus, it is important to understand how the development of IL-4– versus interferon (IFN)-γ–producing NKT cells is regulated. Here, we show that NKT cells from adult blood and those from cord blood undergo massive expansion in cell numbers (500–70,000-fold) during a 4-wk culture with IL-2, IL-7, phytohemagglutinin, anti-CD3, and anti-CD28 mAbs. Unlike adult NKT cells that preferentially produce both IL-4 and IFN-γ, neonatal NKT cells preferentially produce IL-4 after polyclonal activation. Addition of type 2 dendritic cells (DC2) enhances the development of neonatal NKT cells into IL-4+IFN-γ− NKT2 cells, whereas addition of type 1 dendritic cells (DC1) induces polarization towards IL-4−IFN-γ+ NKT1 cells. Adult NKT cells display limited plasticity for polarization induced by DC1 or DC2. Thus, newly generated NKT cells may possess the potent ability to develop into IL-4+IFN-γ− NKT2 cells in response to appropriate stimuli and may thereafter acquire the tendency to produce both IL-4 and IFN-γ

MyD88-dependent expansion of an immature GR-1+CD11b+ population induces T cell suppression and Th2 polarization in sepsis

Polymicrobial sepsis alters the adaptive immune response and induces T cell suppression and Th2 immune polarization. We identify a GR-1+CD11b+ population whose numbers dramatically increase and remain elevated in the spleen, lymph nodes, and bone marrow during polymicrobial sepsis. Phenotypically, these cells are heterogeneous, immature, predominantly myeloid progenitors that express interleukin 10 and several other cytokines and chemokines. Splenic GR-1+ cells effectively suppress antigen-specific CD8+ T cell interferon (IFN) γ production but only modestly suppress antigen-specific and nonspecific CD4+ T cell proliferation. GR-1+ cell depletion in vivo prevents both the sepsis-induced augmentation of Th2 cell–dependent and depression of Th1 cell–dependent antibody production. Signaling through MyD88, but not Toll-like receptor 4, TIR domain–containing adaptor-inducing IFN-β, or the IFN-α/β receptor, is required for complete GR-1+CD11b+ expansion. GR-1+CD11b+ cells contribute to sepsis-induced T cell suppression and preferential Th2 polarization

Социальные функции сельской библиотеки

The paper presents a comparative analysis of social functions of domestic rural libraries in the different periods of their history.Автором дан сравнительный анализ социальных функций отечественных сельских библиотек в различные периоды их истории