Forkhead box P3-positive (Foxp3 + )-inducible Tregs (iTregs) are readily generated by TGF-β1 at low TCR signaling intensity. TGF-β1–mediated Foxp3 expression is further enhanced by retinoic acid (RA) and lactoferrin (LF). However, the intensity of TCR signaling required for induction of Foxp3 expression by TGF-β1 in combination with RA and LF is unknown. Here, we found that either RA or LF alone decreased TGF-β1–mediated Foxp3 expression at low TCR signaling intensity. In contrast, at high TCR signaling intensity, the addition of either RA or LF strongly increased TGF-β1–mediated Foxp3 expression. Moreover, decreased CD28 stimulation was more favorable for TGF-β1/LF–mediated Foxp3 expression. Lastly, we found that at high signaling intensities of both TCR and CD28, combined treatment with TGF-β1, RA, and LF induced robust expression of Foxp3, in parallel with powerful suppressive activity against responder T cell proliferation. Our findings that TGFβ/RA/LF strongly generate high affinity Ag-specific iTreg population would be useful for the control of unwanted hypersensitive immune reactions such as various autoimmune diseases.

Dendritic cells (DCs) are professional antigen-presenting cells (APCs) that initiate both T-cell responses and tolerance. Tolerogenic DCs (tDCs) are regulatory DCs that suppress immune responses through the induction of T-cell anergy and Tregs. Because lactoferrin (LF) was demonstrated to induce functional Tregs and has a protective effect against inflammatory bowel disease, we explored the tolerogenic effects of LF on mouse bone marrow-derived DCs (BMDCs). The expression of CD80/86 and MHC class II was diminished in LF-treated BMDCs (LF-BMDCs). LF facilitated BMDCs to suppress proliferation and elevate Foxp3 +induced Treg (iTreg) differentiation in ovalbumin-specific CD4 + T-cell culture. Foxp3 expression was further increased by blockade of the B7 molecule using CTLA4-Ig but was diminished by additional CD28 stimulation using anti-CD28 Ab. On the other hand, the levels of arginase-1 and indoleamine 2,3-dioxygenase-1 (known as key T-cell suppressive molecules) were increased in LF-BMDCs. Consistently, the suppressive activity of LF-BMDCs was partially restored by inhibitors of these molecules. Collectively, these results suggest that LF effectively causes DCs to be tolerogenic by both the suppression of T-cell proliferation and enhancement of iTreg differentiation. This tolerogenic effect of LF is due to the reduction of costimulatory molecules and enhancement of suppressive molecules.

OBJECTIVES: There is a great deal of interest in the possibility that environmental factors may influence the risk of developing allergic rhinitis (AR) in early life. We investigated the simultaneous effects of mode of delivery and duration of breastfeeding on the development of AR in children. METHODS: Data from 1,374 children participating in the Allergic Rhinitis Cohort Study for kids (ARCO-kids study) was analyzed. All subjects were divided into AR or non-allergic rhinitis (NAR) groups. Data on environmental factors, mode of delivery and duration of breastfeeding were collected using a questionnaire. RESULTS: Compared with short-term breastfeeding (<6 months), long-term breastfeeding (≥12 months) was significantly associated with a lower prevalence of AR (adjusted odds ratio [aOR], 0.54; 95% confidence interval [CI], 0.34 to 0.88). Children in the AR group also had a higher cesarean delivery rate than those in the NAR group (39.1% vs. 32.8%, P=0.05). Regarding the combined effects of mode of delivery and duration of breastfeeding, long-term breastfeeding with a vaginal delivery strongly suppressed the development of AR, compared to short-term breastfeeding with a cesarean delivery (aOR, 0.47; 95% CI, 0.30 to 0.73). CONCLUSION: Long-term breastfeeding (≥12 months) and a vaginal delivery are associated with a lower risk of developing childhood AR.
Breast Feeding ; Cesarean Section ; Child ; Cohort Studies ; Delivery, Obstetric ; Female ; Humans ; Odds Ratio ; Pregnancy ; Prevalence ; Rhinitis ; Rhinitis, Allergic

Porcine epidemic diarrhea (PED) is a highly contagious enteric swine disease. The large economic impact of PED on the swine industry worldwide has made the development of an effective PED vaccine a necessity. S0, a truncated region of the porcine epidemic diarrhea virus (PEDV) spike protein, has been suggested as a candidate antigen for PED subunit vaccines; however, poor solubility problems when the protein is expressed in Escherichia coli, and the inherent problems of subunit vaccines, such as low immunogenicity, remain. Flagellin has been widely used as a fusion partner to enhance the immunogenicity and solubility of many difficult-to-express proteins; however, the conjugation effect of flagellin varies depending on the target antigen or the position of the fusion placement. Here, we conjugated flagellin, Vibrio vulnificus FlaB, to the N- and C-termini of S0 and evaluated the ability of the fusion to enhance the solubility and immunogenicity of S0. Flagellin conjugation in the presence of the trigger factor chaperone tig greatly improved the solubility of the fusion protein (up to 99%) regardless of its conjugation position. Of importance, flagellin conjugated to the N-terminus of S0 significantly enhanced S0-specific humoral immune responses compared to other recombinant antigens in Balb/c mice. The mechanism of this phenomenon was investigated through in vitro and in vivo studies. These findings provide important information for the development of a novel PED vaccine and flagellin-based immunotherapeutics.
Animals ; Diarrhea ; Escherichia coli ; Flagellin ; Immunity, Humoral ; In Vitro Techniques ; Mice ; Porcine epidemic diarrhea virus ; Solubility ; Swine ; Swine Diseases ; Vaccines, Subunit ; Vibrio vulnificus ; Vibrio

γδ T cells are abundant in the gut mucosa and play an important role in adaptive immunity as well as innate immunity. Although γδ T cells are supposed to be associated with the enhancement of Ab production, the status of γδ T cells, particularly in the synthesis of IgA isotype, remains unclear. We compared Ig expression in T cell receptor delta chain deficient (TCRδ⁻/⁻) mice with wild-type mice. The amount of IgA in fecal pellets was substantially elevated in TCRδ⁻/⁻ mice. This was paralleled by an increase in surface IgA expression and total IgA production by Peyer's patches (PPs) and mesenteric lymph node (MLN) cells. Likewise, the TCRδ⁻/⁻ mice produced much higher levels of serum IgA isotype. Here, surface IgA expression and number of IgA secreting cells were also elevated in the culture of spleen and bone marrow (BM) B cells. Germ-line α transcript, an indicator of IgA class switch recombination, higher in PP and MLN B cells from TCRδ⁻/⁻ mice, while it was not seen in inactivated B cells. Nevertheless, the frequency of IgA+ B cells was much higher in the spleen from TCRδ⁻/⁻ mice. These results suggest that γδ T cells control the early phase of B cells, in order to prevent unnecessary IgA isotype switching. Furthermore, this regulatory role of γδ T cells had lasting effects on the long-lived IgA-producing plasma cells in the BM.
Adaptive Immunity ; Animals ; B-Lymphocytes* ; Bone Marrow ; Immunity, Innate ; Immunoglobulin A* ; Immunoglobulin Class Switching* ; Lymph Nodes ; Mice ; Mucous Membrane ; Peyer's Patches ; Plasma Cells ; Receptors, Antigen, T-Cell, gamma-delta ; Recombination, Genetic ; Spleen ; T-Lymphocytes*

BACKGROUND: Although recent studies have investigated the influence of vitamin D on sleep patterns, there is a lack of research on the relationship between vitamin D and sleep patterns in Korean workers. This study focused on the relationship between serum vitamin D levels and sleep in fixed day indoor field workers in the electronics manufacturing industry in Korea. METHODS: The 1472 subjects who were included in this study were selected from fixed day workers in the electronics manufacturing industry who had received a worker’s special health examination at a hospital in Changwon, South Gyeongsang Province between January 2015 and December 2015. Nighttime workers and those who showed symptoms of depression were excluded from this study. The sociodemographic and lifestyle variables of the participants were investigated, including age, sex, marital status, level of education, body mass index, smoking habits, alcohol consumption habits, and regular exercise. Work-related factors were evaluated, such as employee tenure and occupational stress. Serum 25-hydroxyvitamin D was measured as an indicator of vitamin D levels, and quality of sleep was evaluated using the Pittsburgh Sleep Quality Index (PSQI) translated into Korean. RESULTS: The subjects had a mean serum vitamin D level of 13.70 ± 5.93 ng/mL. Vitamin D deficiency, defined as a serum vitamin D level of <10 ng/mL, was found in 24.8% of males and significantly more frequently in females (47.6%). Poor sleep quality was reported by 19.8% of participants with serum vitamin D levels ≥10 ng/mL and by 21.7% of those with serum vitamin D levels <10 ng/mL, which was a significant difference (P = .007). Multiple logistic regression analysis adjusting for significant variables found that poor sleep quality was more likely in those with vitamin D deficiency than those with higher serum vitamin D levels (odds ratio = 1.36; 95% CI, 1.01–1.82). A comparison of serum vitamin D levels and PSQI components showed that the mean scores for subjective sleep quality, sleep latency, and sleep duration were significantly higher in the vitamin D-deficient participants, indicating that the vitamin D-deficient participants had poorer sleep quality. CONCLUSIONS: This study investigated serum vitamin D levels in fixed day indoor field workers in the manufacturing industry in Korea and analyzed the relationship of vitamin D deficiency with sleep quality. A significant correlation was found between serum vitamin D deficiency and poor sleep quality. Based on the results of this study, sleep disorder management for workers can be improved by providing regular examinations checking their serum vitamin D levels and supplying vitamin D to workers with serum vitamin D deficiency to enhance their quality of sleep.
Alcohol Drinking ; Body Mass Index ; Depression ; Education ; Female ; Gyeongsangnam-do ; Health Personnel* ; Humans ; Korea* ; Life Style ; Logistic Models ; Male ; Marital Status ; Sleep Wake Disorders ; Smoke ; Smoking ; Vitamin D Deficiency ; Vitamin D* ; Vitamins*

BACKGROUND AND OBJECTIVES: The skin prick test is a widely used test that uses three methods (allergen/histamine ratio method, erythema size method, and wheal size method) to interpret the results. However, there has been no comparison of these methods. The aim of this study is to compare the three different interpretation methods and define the relationship among them. SUBJECTS AND METHOD: A total of 139 patients who visited our allergy clinic complaining of nasal symptoms were enrolled. Three interpretation methods were used for defining positivity in the skin prick test, and their results were compared. The validity of each interpretation method was evaluated by total nasal symptom score. RESULTS: Positivity in the skin prick test was reported in 48.2% of patients according to the allergen/histamine ratio method and in 64.0% of patients according to the wheal size method and erythema size method. The proportion of subjects who showed a negative result with the allergen/histamine ratio method but positive results with the wheal size method or erythema size method was 15.8%. This group had a significantly higher total nasal symptom score, especially rhinorrhea and nasal obstruction, than subjects who showed negative results on all three methods. CONCLUSION: When diagnosing allergic rhinitis patients using the skin prick test, the wheal size method and erythema size method should be considered rather than the allergen/histamine ratio method.
Diagnosis ; Erythema ; Humans ; Hypersensitivity ; Methods* ; Nasal Obstruction ; Rhinitis, Allergic ; Skin Tests* ; Skin*

PURPOSE: This study attempts to examine the extent to which competencies were identified in a Korean community nursing practice based on the 11 core competencies required by US health nurses. METHODS: This was a descriptive research study, and the subjects of this study were 11 students who were in a four-year nursing course. Data were collected by means of a questionnaire from October 19 to November 22, 2016. RESULTS: Core competencies in total were practiced in 60.0% to 98.5% of schools in Korea. Among these, competencies corresponding to the practice level of ‘high’ were identified as ‘communicating effectively with community nursing subjects and colleagues, and accepting various personal characteristics without criticism or prejudice’. On the other hand, competencies corresponding to the practice level of ‘low’ were identified as ‘to comply with social justice, public good, public health principles, and leadership in a community nursing practice’. CONCLUSION: This study can be used as a resource to categorize the competence of nursing students expected in the field of community nursing. Based on a careful review of core competencies with low practice, it is necessary to seek specific practical strategies to strengthen these competencies in the future.
Community Health Nursing* ; Hand ; Humans ; Korea ; Leadership ; Mental Competency ; Nurses, Public Health* ; Nursing ; Public Health Nursing ; Public Health* ; Social Justice ; Students, Nursing

It is well established that TGF-beta1 and retinoic acid (RA) cause IgA isotype switching in mice. We recently found that lactoferrin (LF) also has an activity of IgA isotype switching in spleen B cells. The present study explored the effect of LF on the Ig production by mouse peritoneal B cells. LF, like TGF-beta1, substantially increased IgA production in peritoneal B1 cells but little in peritoneal B2 cells. In contrast, LF increased IgG2b production in peritoneal B2 cells much more strongly than in peritoneal B1 cells. LF in combination with RA further enhanced the IgA production and, interestingly, this enhancement was restricted to IgA isotype and B1 cells. Similarly, the combination of the two molecules also led to expression of gut homing molecules alpha4beta7 and CCR9 on peritoneal B1 cells, but not on peritoneal B2 cells. Thus, these results indicate that LF and RA can contribute to gut IgA response through stimulating IgA isotype switching and expression of gut-homing molecules in peritoneal B1 cells.
Animals ; B-Lymphocytes ; Immunoglobulin A* ; Immunoglobulin Class Switching ; Immunoglobulin G ; Lactoferrin* ; Mice ; Spleen ; Transforming Growth Factor beta1 ; Tretinoin*

BACKGROUND: The prevalence of anxiety disorders has been increasing in South Korea, with recent studies reporting anxiety disorders as the most common mental disorder among all South Korean females. Anxiety disorders, which are independent risk factors of suicidal ideation and suicide attempts, are significantly correlated with productivity loss, high medical costs, impaired work performance, and frequent worker absence, and thus are potentially serious problems affecting the health of South Korean female workers. In previous studies, anxiety disorders were shown to have a significant correlation with occupational stress. This study seeks to examine the prevalence of anxiety symptoms as well as the relationship between occupational stress and anxiety symptoms among South Korean female manufacturing workers. METHODS: A structured self-reported questionnaire was administered to 1,141 female workers at an electrical appliance manufacturing plant. The questionnaire collected data on general characteristics, health behaviors, sleep quality, job characteristics (shift work, shift work schedule, and job tenure), occupational stress, and anxiety symptoms. Sleep quality was measured using the Pittsburgh Sleep Quality Index, occupational stress with the Korean Occupational Stress Scale-Short Form (KOSS-SF), and anxiety symptoms with the Korean version of the Beck Anxiety Inventory. A chi square test was conducted to determine the distribution differences in anxiety symptoms based on general characteristics, health behaviors, job characteristics, and sleep quality. A linear-by-linear association test was used to determine the distribution differences between anxietysymptoms and the levels of occupational stress. Last, logistic regression analysis was used in order to determine the association between occupational stress and anxiety symptoms. RESULTS: The prevalence of anxiety symptoms was 15.2 %. In the multivariate logistic regression analysis that adjusted for sleep quality and general characteristics, a significantassociation was found for those with anxiety disorders; the odds ratios (OR) were significantly higher the greater the total KOSS-SF score (moderate-risk group OR=2.85, 95 % CI=1.79-4.56; high-risk group OR=5.34, 95 % CI=3.59-7.96). In addition, excluding insufficient job control, all other KOSS-SF subscales were significantly associated with anxiety symptoms, and a relatively high OR was seen in the high-risk group for job demand (OR=3.19, 95 % CI=2.27-4.49), job insecurity (OR=4.52, 95 % CI=2.86-7.13), and occupational culture (OR=4.52, 95 % CI=2.90-7.04). CONCLUSION: There was a significant association between anxiety symptoms and occupational stress stemming from the psychosocial work environment among these South Korean female manufacturing workers. Future longitudinal studies are needed to examine the association between the occupational stress caused by the psychosocial work environment and the incidence of anxiety disorders and anxiety symptoms. Furthermore, intervention programs that aim to address the prevalence of anxiety symptoms and improve the psychosocial work environment, especially for younger female manufacturing workers, are needed.
Anxiety Disorders ; Anxiety* ; Appointments and Schedules ; Efficiency ; Female* ; Health Behavior ; Humans ; Incidence ; Korea ; Logistic Models ; Longitudinal Studies ; Mental Disorders ; Odds Ratio ; Plants ; Prevalence ; Risk Factors ; Suicidal Ideation ; Suicide