Dendritic cells (DCs) are professional antigen-presenting cells that sample their environment and present antigens to naive T lymphocytes for the subsequent antigen-specific immune responses. DCs exist in a range of distinct subpopulations including plasmacytoid DCs (pDCs) and classical DCs (cDCs), with the latter consisting of the cDC1 and cDC2 lineages. Although the roles of DC-specific transcription factors across the DC subsets have become understood, the posttranscriptional mechanisms that regulate DC development are yet to be elucidated. MicroRNAs (miRNAs) are pivotal posttranscriptional regulators of gene expression in a myriad of biological processes, but their contribution to the immune system is just beginning to surface. In this study, our in-house probe collection was screened to identify miRNAs possibly involved in DC development and function by targeting the transcripts of relevant mouse transcription factors. Examination of DC subsets from the culture of mouse bone marrow with Flt3 ligand identified high expression of miR-124 which was able to target the transcript of TCF4, a transcription factor critical for the development and homeostasis of pDCs. Further expression profiling of mouse DC subsets isolated from in vitro culture as well as via ex vivo purification demonstrated that miR-124 was outstandingly expressed in CD24+ cDC1 cells compared to in pDCs and CD172alpha+ cDC2 cells. These results imply that miR-124 is likely involved in the processes of DC subset development by posttranscriptional regulation of a transcription factor(s).
Animals ; Antigen-Presenting Cells ; Biological Processes ; Bone Marrow ; Dendritic Cells* ; Gene Expression ; Homeostasis ; Immune System ; Mice ; MicroRNAs ; RNA Interference ; T-Lymphocytes ; Transcription Factors

Bone marrow-derived dendritic cells (BM-DCs) are generated from bone marrow (BM) cells cultured with granulocyte macrophage-colony stimulating factor (GM-CSF) for a week. In this study we investigated the effect of duration on the BM culture with GM-CSF. Within several months, the cells in the BM culture gradually expressed homogeneous levels of CD11c and major histocompatibility complex II on surface, and they became unable to stimulate allogeneic naïve T cells in mixed lymphocyte reaction (MLR). In addition, when the BM culture were sustained for 32 wk or longer, the BM cells acquired ability to suppress the proliferation of allogeneic T cells in MLR as well as the response of ovalbumin-specific OT-I transgenic T cells in antigen-dependent manner. We found that, except for programmed death-ligand 1, most cell surface molecules were expressed lower in the BM cells cultured with GM-CSF for the extended duration. These results indicate that BM cells in the extended culture with GM-CSF undergo 2 distinct steps of functional change; first, they lose the immunostimulatory capacity; and next, they gain the immunosuppressive ability.
Bone Marrow* ; Dendritic Cells ; Granulocyte-Macrophage Colony-Stimulating Factor ; Granulocytes* ; Immunosuppression ; Lymphocyte Culture Test, Mixed ; Major Histocompatibility Complex ; T-Lymphocytes

To this date, the criteria to distinguish peritoneal macrophages and dendritic cells (DCs) are not clear. Here we delineate the subsets of myeloid mononuclear cells in the mouse peritoneal cavity. Considering phenotypical, functional, and ontogenic features, peritoneal myeloid mononuclear cells are divided into 5 subsets: large peritoneal macrophages (LPMs), small peritoneal macrophages (SPMs), DCs, and 2 MHCII⁺CD11c⁺CD115⁺ subpopulations (i.e., MHCII⁺CD11c⁺CD115⁺CD14⁻CD206⁻ and MHCII⁺CD11c⁺CD115⁺CD14⁺CD206⁺). Among them, 2 subsets of competent Ag presenting cells are demonstrated with distinct functional characteristics, one being DCs and the other being MHCII⁺CD11c⁺CD115⁺CD14⁻CD206⁻ cells. DCs are able to promote fully activated T cells and superior in expanding cytokine producing inflammatory T cells, whereas MHCII⁺CD11c⁺CD115⁺CD14⁻CD206⁻ cells generate partially activated T cells and possess a greater ability to induce Treg under TGF-β and retinoic acid conditions. While the development of DCs and MHCII⁺CD11c⁺CD115⁺CD14⁻CD206⁻ cells are responsive to the treatment of FLT3 ligand and GM-CSF, the number of LPMs, SPMs, and MHCII⁺CD11c⁺CD115⁺CD14⁺CD206⁺ cells are only influenced by the injection of GM-CSF. In addition, the analysis of gene expression profiles among MHCII⁺ peritoneal myeloid mononuclear cells reveals that MHCII⁺CD11c⁺CD115⁺CD14⁺CD206⁺ cells share high similarity with SPMs, whereas MHCII⁺CD11c⁺CD115⁺CD14⁻CD206⁻ cells are related to peritoneal DC2s. Collectively, our study identifies 2 distinct subpopulations of MHCII⁺CD11c⁺CD115⁺ cells, 1) MHCII⁺CD11c⁺CD115⁺CD14⁻CD206⁻ cells closely related to peritoneal DC2s and 2) MHCII⁺CD11c⁺CD115⁺CD14⁺CD206⁺ cells to SPMs.
Animals ; Antigen Presentation ; Dendritic Cells ; Granulocyte-Macrophage Colony-Stimulating Factor ; Macrophages ; Macrophages, Peritoneal ; Mice ; Peritoneal Cavity ; T-Lymphocytes ; Transcriptome ; Tretinoin

The purpose of this study was to examine the association between the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and bone mineral density (BMD). Two large cohort studies were performed: the Dong-gu Study (3,621 men and 5,409 women) and the Namwon Study (3,703 men and 5,672 women). We assessed lumbar spine and femoral neck BMD by dual-energy X-ray absorptiometry. Genotypes were determined by real-time polymerase chain reaction. Multiple linear regression analysis was performed to evaluate the association between MTHFR C677T and BMD, adjusting for age, weight and height. The MTHFR C677T genotype frequencies for CC, CT, and TT genotypes were 34.5, 48.7, and 16.8%, respectively, in the Dong-gu Study and 33.6, 49.2, and 17.2%, respectively, in the Namwon Study. There are no significant differences between the MTHFR C677T genotype and the BMD at the lumbar spine and femoral neck in men or women in both cohorts.
Absorptiometry, Photon ; Aged ; Alleles ; *Bone Density ; Cohort Studies ; Female ; Femur Neck/radiography ; Gene Frequency ; Genotype ; Humans ; Lumbar Vertebrae/radiography ; Male ; Methylenetetrahydrofolate Reductase (NADPH2)/*genetics ; Middle Aged ; Polymorphism, Single Nucleotide

BACKGROUND: Few studies have investigated the association between Apolipoprotein E (APOE) polymorphisms and chronic kidney disease (CKD) in the general population, and their results are inconsistent. METHODS: The current study population was composed of 9,033 subjects aged > or = 50 years who participated in the baseline survey of the Dong-gu Study, which was conducted in Korea between 2007 and 2010. APOE polymorphisms were identified by polymerase chain reaction, and the estimated glomerular filtration rate (eGFR) was calculated using the Modification of Diet in Renal Disease equation. RESULTS: Individuals with the APOE E2 allele had significantly lower total and low density lipoprotein cholesterol levels, those with the APOE E4 allele had lower high density lipoprotein (HDL) cholesterol levels, and those with the APOE E3 allele had lower log-triglyceride levels. Adjusting for covariates (sex, age, body mass index, smoking, systolic blood pressure, hypertension, diabetes, total cholesterol, HDL cholesterol, log-transformed triglycerides, and log-transformed albumin to creatinine ratio), mean eGFR was not significantly different among APOE alleles (E2, 69.4 mL/min/1.73 m2; E3, 69.5 mL/min/1.73 m2; E4, 69.4 ml/min/1.73 m2; P = 0.873). Additionally, the odds ratios (ORs) indicated that APOE polymorphisms were not independent risk factors for CKD (OR, 1.07; 95% confidence interval [CI], 0.91 to 1.26 for the E2 vs. E3 allele; OR, 1.01; 95% CI, 0.88 to 1.16 for the E4 vs. E3 allele). CONCLUSION: APOE polymorphisms were not associated with either eGFR or CKD in the general Korean population.
Alleles ; Apolipoproteins E ; Apolipoproteins* ; Blood Pressure ; Body Mass Index ; Cholesterol ; Cholesterol, HDL ; Cholesterol, LDL ; Creatinine ; Surveys and Questionnaires ; Diet ; Glomerular Filtration Rate ; Hypertension ; Korea ; Lipoproteins ; Odds Ratio ; Polymerase Chain Reaction ; Polymorphism, Genetic ; Renal Insufficiency, Chronic* ; Risk Factors ; Smoke ; Smoking ; Triglycerides

Vitamin D plays an important role in bone metabolism and maintaining bone health. Recently, new evidence has revealed that vitamin D affects chronic diseases such as autoimmune diseases, cardiovascular diseases and certain cancers. The aim of this study was to evaluate the vitamin D status and the prevalence of vitamin D deficiency in an urban Korean population. This study included 8,976 participants (3,587 men and 5,389 women) aged 50 yr and older. Serum 25(OH)D level was measured by chemiluminescent microparticle immunoassay. The prevalence of vitamin D deficiency [25(OH)D < 20 ng/mL] was 59.7% and 86.5% in men and women, respectively. The prevalence of vitamin D deficiency increased significantly with age in men, but not in women and it decreased from April to July, more prominently in men than in women. These results suggest that sun exposure, intake of vitamin D supplement, and regular physical activities is recommended in an urban Koreans, especially in women.
Aged ; Aging ; Bone and Bones/metabolism ; Female ; Humans ; Male ; Middle Aged ; Prevalence ; Republic of Korea/epidemiology ; Risk Factors ; Sex Factors ; Vitamin D/*blood ; Vitamin D Deficiency/blood/*epidemiology

Many studies have investigated relationships between APOE genotype and bone mineral density (BMD). However, the results of these studies have been inconsistent. Few studies have been carried out in Asian populations. We studied the relationship of the APOE gene polymorphism and BMD in two large population-based studies. The datasets included the Dong-gu Study (3575 men and 5335 women) and the Namwon Study (2310 men, 3512 women). Lumbar spine and femoral neck BMD were measured by dual-energy X-ray absorptiometry. APOE genotypes were analyzed by polymerase chain reaction-restriction fragment length polymorphism. The APOE genotypes were classified into APOE E2 (E2/E2 and E2/E3), APOE E3 (E3/E3), and APOE E4 (E3/E4 and E4/E4). The genotype distribution of the study population was in Hardy-Weinberg equilibrium. There were no significant differences among APOE genotype groups in lumbar and femoral neck BMD in either cohort. Our data do not support the hypothesis that the APOE genotype is associated with BMD.
Absorptiometry, Photon ; Apolipoproteins E ; Asian Continental Ancestry Group ; Bone Density ; Cohort Studies ; Dataset ; Female ; Femur Neck ; Genotype ; Humans ; Jeollabuk-do ; Male ; Polymorphism, Genetic ; Spine