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Yong-Jun Liu

Publications and source records attributed to Yong-Jun Liu.

At least 55 records · Page 3Linked to original sources
PubMed2005

Human TSLP promotes CD40 ligand-induced IL-12 production by myeloid dendritic cells but maintains their Th2 priming potential.

Interleukin-4 (IL-4), a major T-helper type 2 (Th2) cytokine, primes dendritic cells (DCs) for IL-12 production, suggesting a negative feedback loop to prevent dysregulated Th2 inflammation, such as allergy. We previously showed that human thymic stromal lymphopoietin (TSLP), highly expressed by keratinocytes of atopic dermatitis, activates CD11c(+) DCs to induce the differentiation of naive CD4(+) and CD8(+) T cells into proallergic effectors. Here we show that TSLP primes DCs to produce large amounts of IL-12 after CD40 ligand stimulation, similar to IL-4 priming of DCs. In contrast to IL-4 priming, DCs activated with TSLP and CD40 ligand induce the differentiation of naive CD4(+) T cells into effectors producing both Th1 and Th2 cytokines, a unique profile that is reminiscent of the late phase of allergy. Thus, TSLP is a major regulatory cytokine for IL-12 production by DCs, and TSLP-activated DCs could promote the persistence of Th2 inflammation even in the presence of IL-12-inducing signals.

CD11c Antigen↗
PubMed2005

IPC: professional type 1 interferon-producing cells and plasmacytoid dendritic cell precursors.

Type 1 interferon-(alpha, beta, omega)-producing cells (IPCs), also known as plasmacytoid dendritic cell precursors (pDCs), represent 0.2%-0.8% of peripheral blood mononuclear cells in both humans and mice. IPCs display plasma cell morphology, selectively express Toll-like receptor (TLR)-7 and TLR9, and are specialized in rapidly secreting massive amounts of type 1 interferon following viral stimulation. IPCs can promote the function of natural killer cells, B cells, T cells, and myeloid DCs through type 1 interferons during an antiviral immune response. At a later stage of viral infection, IPCs differentiate into a unique type of mature dendritic cell, which directly regulates the function of T cells and thus links innate and adaptive immune responses. After more than two decades of effort by researchers, IPCs finally claim their place in the hematopoietic chart as the most important cell type in antiviral innate immunity. Understanding IPC biology holds future promise for developing cures for infectious diseases, cancer, and autoimmune diseases.

Animals↗
PubMed2005

Searching for obesity genes: progress and prospects.

Obesity is a condition of excess body fat that causes or exacerbates several major public health problems. Remarkable progress has been made in the molecular elucidation of monogenic forms of obesity both in rodents and in humans. The most common form of obesity, however, is considered to be a polygenic disorder arising from the interaction of multiple genetic and environmental factors. Identification and characterization of susceptibility genes underlying obesity will contribute to a greater understanding of the pathogenesis of obesity and ultimately will assist in the development of better strategies for prevention and therapeutic intervention. In this article, we discuss the current status and future perspectives for the genetic dissection of obesity, with a focus on the most striking or representative findings.

Animals↗
PubMed2005

Functional diversity and plasticity of human dendritic cell subsets.

The induction of different types of innate and adaptive immune responses, depending on the nature of the antigens and the environmental context, is crucial to cope with a variety of pathogens and concurrently to avoid pathologic reaction to self antigens. Recent studies have elucidated that the diversity of immune responses is critically controlled by dendritic cells (DCs). Two DC subsets, myeloid DCs and plasmacytoid DCs, have been identified in humans. The DC subsets recognize different microbial pathogens by expressing distinct repertoires of Toll-like receptors and induce different types of innate and adaptive immune responses, depending on the environmental factors. In particular, plasmacytoid DC precursors produce vast amounts of type I interferons in response to viruses and thus play an important role in antiviral immunity. Elucidating the cellular and molecular mechanisms that modulate the functions of the 2 DC subsets will lead to an understanding of the pathogenesis of various immune-related diseases and to the development of novel immunologic therapies.

Animals↗
PubMed2005

Bone marrow stromal cells transduced with human hemangiopoietin gene support hematopoiesis in vitro.

BACKGROUND AND OBJECTIVES: The aim of this study was to construct a eukaryotic expression vector containing human hemangiopoietin (hHAPO) gene and express it in mouse bone marrow stromal cell line HESS-5, then support hematopoiesis in vitro with gene-modified HESS-5 (hHAPO-HESS-5). DESIGN AND METHODS: The polymerase chain reaction (PCR) products of HAPO were digested with BamHI and BgII. Then the HAPO gene segment obtained was again cloned into pIRES2-EGFP to construct recombinant eukaryotic expression vector HAPO-pIRES2-EGFP. The recombinant vector was identified by enzyme digestion analysis, PCR, and sequencing. HESS-5 cells were transformed by recombinant vector and positive clones were selected with G418. The expression of HAPO gene in the transformed cells was detected by studying EGFP expression, reverse transcription (RT)-PCR, and Western-blotting analysis. Support of human hematopoiesis by hHAPO-HESS-5 cells was evaluated in co-culture experiments with human CD34+ cells. RESULTS: Enzyme digestion analysis and sequencing showed that the target gene had been cloned into the recombinant vector. The expression of HAPO gene in the transformed stromal cells was demonstrated by fluoro-microscopy and RT-PCR analysis. HAPO protein was also detected in the supernatant of hHAPO-HESS-5 by Western blot analysis. As expected, stably transfected hHAPO-HESS-5 cells significantly increased in both relative and absolute numbers of CD34+ cells after 14 days of culture. The PKH26 study demonstrated that cell division was faster in CD34+ cells co-cultured with hHAPO-HESS-5 cells than in cells cocultured with vector-HESS-5 cells. The hHAPO-HESS-5 cells also supported human hematopoiesis in vitro more efficiently than did control vector-HESS-5 cells. INTERPRETATION AND CONCLUSIONS: A recombinant eukaryotic expression vector has been constructed and expressed successfully in transformed cells. The hHAPO-HESS-5 cells support rapid generation of primitive progenitor cells and maintain reconstituting ability of hematopoietic stem cells in vitro. Therefore, it would be possible to use stromal cells expressing HAPO gene as seed cells in the bone marrow transplantation.

Angiopoietins↗
PubMed2005

[High expression of mirobial transglutaminase gene from Streptoverticillium mobaraense in Escherichia coli].

The microbial transglutamunase (MTG) gene was amplified from the genomic DNA of Streptoverticillium mobaraensea by using PCR and inserted into pET vector to construct the expression plasmid called pET-MTG. The pET-MTG was transfected into E. coli (Rosetta DE3) and the MTG protein was found to be highly expressed as inclusion bodies. The inclusion bodies were isolated and subjected to denaturation and re-naturation, followed by strong cation ion-exchange chromatography to purify the expressed MTG. The specific activity of purified MTG was close to that of native MTG. Taken together, this study might provide a base for the industrial production of microbial transglutaminase.

Bacterial Proteins↗
PubMed2005

Alpha2-HS glycoprotein gene is associated with bone size at the hip in Chinese.

Bone size is an important risk factor, independent of bone mineral density (BMD), for osteoporotic fracture. Bone size has a high heritability. A better understanding of genetic factors regulating bone size will have important clinical implications. In this study, we explored the relationship between the alpha2-HS glycoprotein (AHSG) gene and bone size variation at the spine and hip in a Chinese population. The study sample comprised 1 260 subjects from 401 Chinese nuclear families (each including both parents and at least one female child). The Sac / polymorphism inside the exon 7 of the AHSG gene was genotyped and analyzed. This variant represents a nucleotide substitution of C to G at amino acid position 238 resulting in a translation polymorphism of threonine to serine and thus making a potential impact on gene function. We assessed population stratification but did not find significant evidence at any skeletal sites. We found significant association between the AHSG Sac / polymorphism and bone size at the intertrochanteric region (P = 0.019) and the total hip (P = 0.035). The polymorphisms explained 3.74% and 3.16% variations in bone size at the intertrochanteric region and total hip respectively. No significant evidence of linkage was detected, largely due to the limited number of sibpairs in this data set and less informative marker (AHSG Sac / polymorphism) (compared with microsatellite markers) for linkage analysis. Our results suggested that the AHSG gene may contribute to bone size variation at the hip in this Chinese population.

Asian People↗
PubMed2004

Plasmacytoid dendritic cell precursors/type I interferon-producing cells sense viral infection by Toll-like receptor (TLR) 7 and TLR9.

Plasmacytoid dendritic cell (pDC) precursors, also called type I IFN (alpha/beta/omega)-producing cells (IPCs), are the key effectors in the innate immune system because of their extraordinary capacity to produce type I IFNs against microbial infection, particularly viral infection. In contrast to myeloid DCs, human pDC/IPCs selectively express Toll-like receptor (TLR) 7 and TLR9 within the endosomal compartment. These receptors are specifically designed to recognize the nucleoside-based products derived from RNA viruses and DNA viruses. Therefore, this expression profile potentially enables pDC/IPCs to sense a variety of viruses. Stimulation of TLR7 or TLR9 leads to type I IFN responses through the MyD88 pathway. Thus, pDC/IPCs may play a central role in host defense against viral infection through the TLR7 and TLR9 system.

Animals↗
PubMed2004

Human plasmacytoid dendritic cells activated by CpG oligodeoxynucleotides induce the generation of CD4+CD25+ regulatory T cells.

Plasmacytoid dendritic cells (PDCs) are key effectors in host innate immunity and orchestrate adaptive immune responses. CpG oligodeoxynucleotides (ODN) have potent immunostimulatory effects on PDCs through TLR9 recognition and signaling. Little is known about the effects of CpG ODN on human PDC-mediated T cell priming. Here we show that type B CpG ODN effectively promotes PDCs to prime allogeneic naive CD4(+)CD25(-) T cells to differentiate into CD4(+)CD25(+) regulatory T (Treg) cells. The CD4(+)CD25(+) T cells induced by CpG ODN-activated PDCs express forkhead transcription factor 3 and produce IL-10, TGF-beta, IFN-gamma, and IL-6, but low IL-2 and IL-4. These CD4(+)CD25(+) T cells are hyporesponsive to secondary alloantigen stimulation and strongly inhibit proliferation of autologous or allogeneic naive CD4(+) T cells in an Ag-nonspecific manner. CpG ODN-activated PDCs require direct contact with T cells to induce CD4(+)CD25(+) Treg cells. Interestingly, IL-10 and TGF-beta were undetectable in the supernatants of CpG ODN-stimulated PDC cultures. Both CpG-A and CpG-C ODN-activated PDCs similarly induced the generation of CD4(+)CD25(+) Treg cells with strong immune suppressive function. This study demonstrates that TLR9 stimulation can promote PDC-mediated generation of CD4(+)CD25(+) Treg cells and suggests PDCs may play an important role in the maintenance of immunological tolerance.

Adjuvants, Immunologic↗
PubMed2004

Quantifying the relationship between gene expressions and trait values in general pedigrees.

Treating mRNA transcript abundances as quantitative traits and examining their relationships with clinical traits have been pursued by using an analytical approach of quantitative genetics. Recently, Kraft et al. presented a family expression association test (FEXAT) for correlation between gene expressions and trait values with a family-based (sibships) design. This statistic did not account for biological relationships of related subjects, which may inflate type I error rate and/or decrease power of statistical tests. In this article, we propose two new test statistics based on a variance-components approach for analyses of microarray data obtained from general pedigrees. Our methods accommodate covariance between relatives for unmeasured genetic effects and directly model covariates of clinical importance. The efficacy and validity of our methods are investigated by using simulated data under different sample sizes, family sizes, and family structures. The proposed LR method has correct type I error rate with moderate to large sample sizes regardless of family structure and family sizes. It has higher power with complex pedigrees and similar power to the FEXAT with sibships. The other proposed FEXAT(R) method is favorable with large family sizes, regardless of sample sizes and family structure. Our methods, robust to population stratification, are complementary to the FEXAT in expression-trait association studies.

Animals↗
PubMed2004

APOE haplotypes influence bone mineral density in Caucasian males but not females.

Low bone mineral density (BMD) is one of the most important risk factors for osteoporosis. Apolipoprotein E (APOE) has been considered as a candidate gene for osteoporosis because of its influence on osteoblast uptake of lipoprotein-borne vitamin K. Using the quantitative transmission disequilibrium test QTDT, we examined linkage and/or association of APOE and BMD at the lumbar spine and the total hip in a sample of 387 Caucasian nuclear families with 715 parents and 953 children. The children were aged 20-50 years and female offspring were premenopausal as well. Four single nucleotide polymorphisms (SNP1-4) in the APOE gene, 4-locus haplotypes and 2-locus haplotypes (epsilon1, epsilon2, epsilon3, epsilon4 isoforms, reconstructed by SNP3 and SNP4) were analyzed. In the whole sample and the female offspring families we found no evidence of linkage or association for either single SNP or haplotype with BMD at the two studied skeletal sites. In the male offspring families, within-family associations were observed at the haplotypes CGTC (P = 0.001), GGTT (P = 0.002), and GATC (P = 0.006) for the lumbar spine BMD, and GATC (P = 0.008) for the total hip BMD. These data suggested that in our studied Caucasian population, APOE may have effects on BMD variation in males but not females. Further studies with a larger sample size are required to confirm such results.

Absorptiometry, Photon↗
PubMed2004

Patterns of linkage disequilibrium and haplotype distribution in disease candidate genes.

BACKGROUND: The adequacy of association studies for complex diseases depends critically on the existence of linkage disequilibrium (LD) between functional alleles and surrounding SNP markers. RESULTS: We examined the patterns of LD and haplotype distribution in eight candidate genes for osteoporosis and/or obesity using 31 SNPs in 1,873 subjects. These eight genes are apolipoprotein E (APOE), type I collagen alpha1 (COL1A1), estrogen receptor-alpha (ER-alpha), leptin receptor (LEPR), parathyroid hormone (PTH)/PTH-related peptide receptor type 1 (PTHR1), transforming growth factor-beta1 (TGF-beta1), uncoupling protein 3 (UCP3), and vitamin D (1,25-dihydroxyvitamin D3) receptor (VDR). Yin yang haplotypes, two high-frequency haplotypes composed of completely mismatching SNP alleles, were examined. To quantify LD patterns, two common measures of LD, D' and r2, were calculated for the SNPs within the genes. The haplotype distribution varied in the different genes. Yin yang haplotypes were observed only in PTHR1 and UCP3. D' ranged from 0.020 to 1.000 with the average of 0.475, whereas the average r2 was 0.158 (ranging from 0.000 to 0.883). A decay of LD was observed as the intermarker distance increased, however, there was a great difference in LD characteristics of different genes or even in different regions within gene. CONCLUSION: The differences in haplotype distributions and LD patterns among the genes underscore the importance of characterizing genomic regions of interest prior to association studies.

Apolipoproteins E↗
PubMed2004

Genome scan for QTLs underlying bone size variation at 10 refined skeletal sites: genetic heterogeneity and the significance of phenotype refinement.

To identify quantitative trait loci (QTLs) underlying variation in bone size, we conducted a whole-genome linkage scan in 53 pedigrees with 630 subjects using 380 microsatellite markers. Lumbar area 1, 2, 3, and 4 at the spine, femoral neck, trochanter, intertrochanter areas at the hip, ultradistal, mid-distal, and one-third distal areas at the wrist were measured by dual-energy X-ray absorptiometry (DXA), and adjusted for age, height, weight, and sex. Two-point and multipoint linkage analyses were performed for skeletal bone size at each site and their composite measurements using the SOLAR package. Two chromosomal regions (1q22 and 10q21) were identified with significant evidence of linkage (LOD > 4.32) to one-third distal area, and three were identified with suggestive evidence of linkage (LOD > 2.93) to bone size in one skeletal site. Our results indicated that the low power of QTLs mapping for composite phenotypic measurements may result from genetic heterogeneity of complex traits.

Bone and Bones↗
PubMed2004

Structure and reactivity of mixed omega-carboxyalkyl/alkyl monolayers on silicon: ATR-FTIR spectroscopy and contact angle titration.

The structure, reactivity, and acid-base properties of mixed monolayers prepared by photochemical reaction of hydrogen-terminated silicon with mixtures of ethyl undecylenate and n-alkenes were studied by ATR-FTIR spectroscopy and contact-angle measurements. The surface composition of the mixed monolayers and its correlation with the hydrolysis reactivity of terminal ethoxycarbonyl (ester) groups were investigated by systematically varying the mole fraction of ethyl undecylenate and the chain length of the unsubstituted alkenes in the binary deposition solution. It has been shown that the mole fraction of ester groups on the surface deviates only slightly from the mole fraction of ethyl undecylenate in the solution. The efficiency of ester hydrolysis under acidic conditions is significantly influenced by the monolayer structure, i.e., the surface density of ester groups and length of the unsubstituted alkyl chains. In addition, we find that mixed omega-alkanoic acid/alkyl monolayers on silicon (prepared via hydrolysis) exhibit well-defined contact angle titration curves from which the surface acid dissociation constants were determined. The results were compared with the acid-base properties reported in the literature for carboxylic acid-terminated alkylsiloxane monolayers on hydroxylated silicon and for omega-mercaptoalkanoic acid/alkanethiolate monolayers on gold. The weak pKa dependence (deltapKa approximately 1) on the surface density of carboxylic acid groups and on the length of unsubstituted alkyl chains is attributed to variations of the microenvironment of the acid moieties. These experimental findings provide fundamental knowledge at the molecular level for the preparation of bioreactive surfaces of controlled reactivity on crystalline semiconductor substrates.

Journal Article↗
PubMed2004

Tests of linkage and/or association of the LEPR gene polymorphisms with obesity phenotypes in Caucasian nuclear families.

Genetic variations in the leptin receptor (LEPR) gene have been conceived to affect body weight in general populations. In this study, using the tests implemented in the statistical package QTDT, we evaluated association and/or linkage of the LEPR gene with obesity phenotypes in a large sample comprising 1,873 subjects from 405 Caucasian nuclear families. Obesity phenotypes tested include body mass index (BMI), fat mass, percentage fat mass (PFM), and lean mass, with the latter three measured by dual-energy X-ray absorptiometry (DXA). Three single nucleotide polymorphisms (SNPs), namely Lys109Arg (A/G), Lys656Asn (G/C), Pro1019Pro (G/A), in the LEPR gene were analyzed. Significant linkage disequilibrium (0.394 < or = |D'| < or = 0.688, P < 0.001) was observed between pairs of the three SNPs. No significant population stratification was found for any SNP/phenotype. In single-locus analyses, evidence of association was observed for Lys656Asn with lean mass (P = 0.002) and fat mass (P = 0.015). The contribution of this polymorphism to the phenotypic variation of lean mass and fat mass was 2.63% and 1.15%, respectively. Subjects carrying allele G at the Lys656Asn site had, on average, 3.16% higher lean mass and 2.71% higher fat mass than those without it. In the analyses for haplotypes defined by the three SNPs, significant associations were detected between haplotype GCA (P = 0.005) and lean mass. In addition, marginally significant evidence of association was observed for this haplotype with fat mass (P = 0.012). No statistically significant linkage was found, largely due to the limited power of the linkage approach to detect small genetic effects in our data sets. Our results suggest that the LEPR gene polymorphisms contribute to variation in obesity phenotypes.

Adult↗
PubMed2004

Human thymic stromal lymphopoietin promotes dendritic cell-mediated CD4+ T cell homeostatic expansion.

T cell homeostasis is a self-regulating process for maintaining the size of the peripheral T cell pool. Although dendritic cells (DCs) seem to be important in T cell homeostasis, the molecular regulation of DC-mediated T cell homeostasis is unknown. We show that human DCs activated by thymic stromal lymphopoietin (TSLP) induced a robust expansion of autologous CD4(+) T cell populations, which depended on self peptide-major histocompatibility complex. The proliferating T cells adopted and maintained a central memory polyclonal phenotype and could differentiate into T helper type 1 or type 2 effector cells. These results, together with findings of TSLP expression in epithelial cells of mucosal lymphoid tissues and thymus, indicate that TSLP is involved in DC-mediated CD4(+) T cell homeostasis.

Animals↗
PubMed2004

Current limitations of SNP data from the public domain for studies of complex disorders: a test for ten candidate genes for obesity and osteoporosis.

BACKGROUND: Public SNP databases are frequently used to choose SNPs for candidate genes in the association and linkage studies of complex disorders. However, their utility for such studies of diseases with ethnic-dependent background has never been evaluated. RESULTS: To estimate the accuracy and completeness of SNP public databases, we analyzed the allele frequencies of 41 SNPs in 10 candidate genes for obesity and/or osteoporosis in a large American-Caucasian sample (1,873 individuals from 405 nuclear families) by PCR-invader assay. We compared our results with those from the databases and other published studies. Of the 41 SNPs, 8 were monomorphic in our sample. Twelve were reported for the first time for Caucasians and the other 29 SNPs in our sample essentially confirmed the respective allele frequencies for Caucasians in the databases and previous studies. The comparison of our data with other ethnic groups showed significant differentiation between the three major world ethnic groups at some SNPs (Caucasians and Africans differed at 3 of the 18 shared SNPs, and Caucasians and Asians differed at 13 of the 22 shared SNPs). This genetic differentiation may have an important implication for studying the well-known ethnic differences in the prevalence of obesity and osteoporosis, and complex disorders in general. CONCLUSION: A comparative analysis of the SNP data of the candidate genes obtained in the present study, as well as those retrieved from the public domain, suggests that the databases may currently have serious limitations for studying complex disorders with an ethnic-dependent background due to the incomplete and uneven representation of the candidate SNPs in the databases for the major ethnic groups. This conclusion attests to the imperative necessity of large-scale and accurate characterization of these SNPs in different ethnic groups.

Asian People↗