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Yong-Jun Liu

Publications and source records attributed to Yong-Jun Liu.

89 records · Page 5Linked to original sources
PubMed2003

Activation of influenza virus-specific CD4+ and CD8+ T cells: a new role for plasmacytoid dendritic cells in adaptive immunity.

Plasmacytoid dendritic cells (pDCs) contribute to innate antiviral immune responses by producing type I interferons (IFNs) upon exposure to enveloped viruses. However, their role in adaptive immune responses, such as the initiation of antiviral T-cell responses, is not known. In this study, we examined interactions between blood pDCs and influenza virus with special attention to the capacity of pDCs to activate influenza-specific T cells. pDCs were compared with CD11c(+) DCs, the most potent antigen-presenting cells (APCs), for their capacity to activate T-cell responses. We found that like CD11c(+) DCs, pDCs mature following exposure to influenza virus, express CCR7, and produce proinflammatory chemokines, but differ in that they produce type I IFN and are resistant to the cytopathic effect of the infection. After influenza virus exposure, both DC types exhibited an equivalent efficiency to expand anti-influenza virus cytotoxic T lymphocytes (CTLs) and T helper 1 (TH1) CD4(+) T cells. Our results pinpoint a new role of pDCs in the induction of antiviral T-cell responses and suggest that these DCs play a prominent role in the adaptive immune response against viruses.

Antigen Presentation↗
PubMed2003

Molecular studies of identification of genes for osteoporosis: the 2002 update.

We aim to give a comprehensive review, updated to 2002, of the most important and representative molecular genetic studies, performed mainly within the past decade, that aimed to identify the gene(s) involved in osteoporosis. Early reviews were largely confined to association studies in humans, but we review here, separately, the results of both association and linkage studies in humans, and quantitative trait locus (QTL) mapping in animal models. The main results of all the studies are tabulated for comparison and ease of reference, and to provide a comprehensive retrospective view of molecular genetics studies of osteoporosis. The most striking findings and the most representative studies are singled out for comment regarding the immediacy of their influence on present understanding of the genetics of osteoporosis and on the current status of genetic research in osteoporosis. This is particularly relevant for studies on the association of the vitamin D receptor (VDR) gene, for which there has been a large body of studies and reviews published. The format adopted by this review should be ideal for accommodating future new advances and studies in a fairly young field that is still developing rapidly.

Animals↗
PubMed2003

Molecular and genetic mechanisms of obesity: implications for future management.

Obesity has become a worldwide public health problem affecting millions of people. A disruption of the balance between energy intake and energy expenditure is believed to be the major cause of obesity. Substantial progress has been made in deciphering the pathogenesis of energy homeostasis over the past few years. The fact that obesity is under strong genetic control has been well established. Human monogenic obesity is rare in large populations, the most common form of obesity is considered to be a polygenic disorder arising from the interaction of multiple genetic and environmental factors. Here, we attempt to briefly review the most recent understanding of molecular mechanisms involved in energy homeostasis and adipogenesis. We discuss the advantages and disadvantages of various approaches commonly used in search for susceptibility genes for obesity. The main results from these genetic studies are summarized, with comments made on the most striking or representative findings. Finally, the implications of the recent advances in the understanding of molecular genetic mechanisms of body weight regulation on prevention and therapeutic intervention of obesity will be discussed.

Adipose Tissue↗
PubMed2002

A whole-genome linkage scan suggests several genomic regions potentially containing QTLs underlying the variation of stature.

Human height is a complex trait under the control of both genetic and environment factors. In order to identify genomic regions underlying the variation of stature, we performed a whole-genome linkage analysis on a sample of 53 human pedigrees containing 1,249 sib pairs, 1,098 grandparent-grandchildren pairs, 1,993 avuncular pairs, and 1,172 first-cousin pairs. Several genomic regions were suggested by our study to be linked with human height variation. These regions include 5q31 at 144 cM from pter on chromosome 5 (with a maximum LOD score of 2.14 in multipoint linkage analyses), Xp22 at the marker DXS1060, and Xq25 at DXS1001 on the X chromosome (with LOD scores of 1.95 and 1.91, respectively, in two-point linkage analyses). Noticeably, Xp22 happens to be the very region where a newly identified gene underlying idiopathic short stature, SHOX, maps. Based on our findings, further confirmation and fine-mapping studies are to be pursued on expanded samples and/or with denser markers for eventual identification of major functional genes involved in human height variation.

Body Height↗
PubMed2002

Human epithelial cells trigger dendritic cell mediated allergic inflammation by producing TSLP.

Whether epithelial cells play a role in triggering the immune cascade leading to T helper 2 (T(H)2)-type allergic inflammation is not known. We show here that human thymic stromal lymphopoietin (TSLP) potently activated CD11c(+) dendritic cells (DCs) and induced production of the T(H)2-attracting chemokines TARC (thymus and activation-regulated chemokine; also known as CCL17) and MDC (macrophage-derived chemokine; CCL22). TSLP-activated DCs primed naïve T(H) cells to produce the proallergic cytokines interleukin 4 (IL-4), IL-5, IL-13 and tumor necrosis factor-alpha, while down-regulating IL-10 and interferon-gamma. TSLP was highly expressed by epithelial cells, especially keratinocytes from patients with atopic dermatitis. TSLP expression was associated with Langerhans cell migration and activation in situ. These findings shed new light on the function of human TSLP and the role played by epithelial cells and DCs in initiating allergic inflammation.

Adult↗
PubMed2002

Modulation of dendritic cell differentiation and maturation by decoy receptor 3.

Decoy receptor 3 (DcR3), a soluble receptor belonging to the TNFR superfamily, is a receptor for both Fas ligand (FasL) and LIGHT. It has been demonstrated that DcR3 is up-regulated in lung and colon cancers, thus promoting tumor growth by neutralizing the cytotoxic effects of FasL and LIGHT. In this study, we found that DcR3.Fc profoundly modulated dendritic cell differentiation and maturation from CD14(+) monocytes, including the up-regulation of CD86/B7.2, and the down-regulation of CD40, CD54/ICAM-1, CD80/B7.1, CD1a, and HLA-DR. Moreover, DcR3-treated dendritic cells suppressed CD4(+) T cell proliferation in an allogeneic MLR and up-regulated IL-4 secretion of CD4(+)CD45RA(+) T cells. This suggests that DcR3.Fc may act not only as a decoy receptor to FasL and LIGHT, but also as an effector molecule to skew T cell response to the Th2 phenotype.

Adjuvants, Immunologic↗
PubMed2002

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-alpha, 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-alpha 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.

Animals↗
PubMed2002

A genomewide linkage scan for quantitative-trait loci for obesity phenotypes.

Obesity is an increasingly serious health problem in the world. Body mass index (BMI), percentage fat mass, and body fat mass are important indices of obesity. For a sample of pedigrees that contains >10,000 relative pairs (including 1,249 sib pairs) that are useful for linkage analyses, we performed a whole-genome linkage scan, using 380 microsatellite markers to identify genomic regions that may contain quantitative-trait loci (QTLs) for obesity. Each pedigree was ascertained through a proband who has extremely low bone mass, which translates into a low BMI. A major QTL for BMI was identified on 2q14 near the marker D2S347 with a LOD score of 4.04 in two-point analysis and a maximum LOD score (MLS) of 4.44 in multipoint analysis. The genomic region near 2q14 also achieved an MLS >2.0 for percentage of fat mass and body fat mass. For the putative QTL on 2q14, as much as 28.2% of BMI variation (after adjustment for age and sex) may be attributable to this locus. In addition, several other genomic regions that may contain obesity-related QTLs are suggested. For example, 1p36 near the marker D1S468 may contain a QTL for BMI variation, with a LOD score of 2.75 in two-point analysis and an MLS of 2.09 in multipoint analysis. The genomic regions identified in this and earlier reports are compared for further exploration in extension studies that use larger samples and/or denser markers for confirmation and fine-mapping studies, to eventually identify major functional genes involved in obesity.

Adipose Tissue↗
PubMed2002

Generation of human CD8 T regulatory cells by CD40 ligand-activated plasmacytoid dendritic cells.

Although CD8 T cell-mediated immunosuppression has been a well-known phenomenon during the last three decades, the nature of primary CD8 T suppressor cells and the mechanism underlying their generation remain enigmatic. We demonstrated that naive CD8 T cells primed with allogeneic CD40 ligand-activated plasmacytoid dendritic cells (DC)2 differentiated into CD8 T cells that displayed poor secondary proliferative and cytolytic responses. By contrast, naive CD8 T cells primed with allogeneic CD40 ligand-activated monocyte-derived DCs (DC1) differentiated into CD8 T cells, which proliferated to secondary stimulation and killed allogeneic target cells. Unlike DC1-primed CD8 T cells that produced large amounts of interferon (IFN)-gamma upon restimulation, DC2-primed CD8 T cells produced significant amounts of interleukin (IL)-10, low IFN-gamma, and no IL-4, IL-5, nor transforming growth factor (TGF)-beta. The addition of anti-IL-10-neutralizing monoclonal antibodies during DC2 and CD8 T cell coculture, completely blocked the generation of IL-10-producing anergic CD8 T cells. IL-10-producing CD8 T cells strongly inhibit the allospecific proliferation of naive CD8 T cells to monocytes, and mature and immature DCs. This inhibition was mediated by IL-10, but not by TGF-beta. IL-10-producing CD8 T cells could inhibit the bystander proliferation of naive CD8 T cells, provided that they were restimulated nearby to produce IL-10. IL-10-producing CD8 T cells could not inhibit the proliferation of DC1-preactivated effector T cells. This study demonstrates that IL-10-producing CD8 T cells are regulatory T cells, which provides a cellular basis for the phenomenon of CD8 T cell-mediated immunosuppression and suggests a role for plasmacytoid DC2 in immunological tolerance.

CD40 Ligand↗
PubMed2002

Mutation patterns at dinucleotide microsatellite loci in humans.

Microsatellites are a major type of molecular markers in genetics studies. Their mutational dynamics are not clear. We investigated the patterns and characteristics of 97 mutation events unambiguously identified, from 53 multigenerational pedigrees with 630 subjects, at 362 autosomal dinucleotide microsatellite loci. A size-dependent mutation bias (in which long alleles are biased toward contraction, whereas short alleles are biased toward expansion) is observed. There is a statistically significant negative relationship between the magnitude (repeat numbers changed during mutation) and direction (contraction or expansion) of mutations and standardized allele size. Contrasting with earlier findings in humans, most mutation events (63%) in our study are multistep events that involve changes of more than one repeat unit. There was no correlation between mutation rate and recombination rate. Our data indicate that mutational dynamics at microsatellite loci are more complicated than the generalized stepwise mutation models.

Alleles↗
PubMed2002

Natural type I interferon-producing cells as a link between innate and adaptive immunity.

Type I interferons (IFNs) are promptly produced upon invasion of pathogens, and activate a broad range of effector cells in the innate and adaptive immune system. Lin(-)CD4(+)CD11c(-) plasmacytoid dendritic cell precursors (plasmacytoid pre-DCs) produce enormous amounts of type I IFNs in response to viruses and CpG DNA, thus corresponding to the previously described but not fully defined natural type I IFN-producing cells (IPCs). Plasmacytoid pre-DCs strongly express toll-like receptor (TLR) 7 and TLR9, in contrast to monocytes, which mainly express TLR1, 2, 4, 5, and 8, suggesting that these two DC precursors recognize different microbial molecules and that they may have developed through different evolutionary trails. Three different stimuli, CpG DNA plus CD40 ligand, interleukin-3 (IL-3), and herpes simplex virus, stimulate plasmacytoid pre-DCs to differentiate into DCs that induce distinct types of T helper cells, i.e., Th1, Th2, and IFN-gamma- and IL-10-producing T cells, respectively. The remarkable versatility of plasmacytoid pre-DCs distinguishes them from other cell types in the immune system that have only limited functions, and suggests that these cells may play a key role in integrating the innate and adaptive aspects of various immune responses.

Cell Differentiation↗
PubMed2002

Human plasmacytoid-derived dendritic cells and the induction of T-regulatory cells.

Suppression by T-regulatory (Tr) cells is essential for the induction of T-cell tolerance and the prevention of autoimmune diseases, organ rejection, and graft-versus-host disease. Increasing attention has been devoted to understand the role of dendritic cells (DC) in the control of Tr-cell differentiation. Here we review the recent evidence that cluster designation (CD)40-ligand activated plasmacytoid-derived DCs (DC2) have the ability to induce primary Tr-cell differentiation. We propose that in addition to the regulatory functions of immature myeloid DC, Tr-cell induction by DC2 represents a nonredundant mechanism for the safeguard of peripheral T-cell tolerance. DC2 can be used as tool to drive potent antigen specific Tr-cell differentiation and expansion in vitro and in vivo.

CD4-Positive T-Lymphocytes↗
PubMed2002

Natural type 1 interferon producing cells in HIV infection.

Natural type 1 interferon producing cells (IPCs) are in the first line of defense against infectious pathogens. Besides the known properties of type 1 interferons in inhibiting human immunodeficiency virus (HIV) replication, the recent characterization of human IPCs and the possibility to purify them for in vitro studies has greatly accelerated the study of their role in HIV infection. The blood IPC numbers and function are decreased in HIV primary infection and in advanced stages of HIV infection. Loss of circulating IPCs correlates with a high HIV viral load and the occurrence of opportunistic infections. Moreover, HIV can directly infect IPCs in vitro, providing a potential explanation for their in vivo depletion. Thus, the balance between IPCs and HIV replication might be critical in determining the control or progression of HIV infection.

AIDS-Related Opportunistic Infections↗
PubMed2002

Mouse and human dendritic cell subtypes.

Dendritic cells (DCs) collect and process antigens for presentation to T cells, but there are many variations on this basic theme. DCs differ in the regulatory signals they transmit, directing T cells to different types of immune response or to tolerance. Although many DC subtypes arise from separate developmental pathways, their development and function are modulated by exogenous factors. Therefore, we must study the dynamics of the DC network in response to microbial invasion. Despite the difficulty of comparing the DC systems of humans and mice, recent work has revealed much common ground.

Animals↗
PubMed2002

A whole-genome linkage scan suggests several genomic regions potentially containing quantitative trait Loci for osteoporosis.

Osteoporosis is an important health problem, particularly in the elderly women. Bone mineral density (BMD) is a major determinant of osteoporosis. For a sample of 53 pedigrees that contain 1249 sibling pairs, 1098 grandparent-grandchildren pairs, and 2589 first cousin pairs, we performed a whole- genome linkage scan using 380 microsatellite markers to identify genomic regions that may contain quantitative trait loci (QTL) of BMD. Each pedigree was ascertained through a proband with BMD values belonging to the bottom 10% of the population. We conducted two-point and multipoint linkage analyses. Several potentially important genomic regions were suggested. For example, the genomic region near the marker D10S1651 may contain a QTL for hip BMD variation (with two-point analysis LOD score of 1.97 and multipoint analysis LOD score of 2.29). The genomic regions near the markers D4S413 and D12S1723 may contain QTLs for spine BMD variation (with two-point analysis LOD score of 2.12 and 2.17 and multipoint analysis LOD score of 3.08 and 2.96, respectively). The genomic regions identified in this and some earlier reports are compared for exploration in extension studies with larger samples and/or denser markers for confirmation and fine mapping to eventually identify major functional genes involved in osteoporosis.

Bone Density↗