Subject(s)
Glaucoma , Optic Disk , Humans , Optic Disk/blood supply , Retina , Glaucoma/etiology , Choroid/blood supplyABSTRACT
AIM: To explain the process taken by Chinese family care partners of older adults in the Greater Toronto Area, Canada, to access health and social services in their communities. The research question was: What mechanisms and structures impact the agency of Chinese family care partners of older adults, in the process of assisting them to access health and social services? DESIGN: This qualitative study was informed by critical realism. METHODS: Chinese family care partners of older adults in the Greater Toronto Area, Canada, were interviewed from August 2020 to June 2021. Transcripts underwent thematic analysis. FINDINGS: Twenty-eight Chinese family care partners expressed a firm commitment to maintain caregiving conditions and to judiciously access health and social services. Their commitment was made up of three parts: (a) legislative and cultural norms of family, work, and society; (b) their perseverance to fill gaps with limited social and financial resources; (c) the quality of their relationship to, and illness trajectory of the older adults. The social structures created tension in how Chinese family care partners made decisions, negotiated resources, and ultimately monitored and coordinated timely access with older adults. CONCLUSION: Participants' commitment and perseverance were conceptualized as "grit," central to their agency to conform to legislative and cultural norms. Moreover, findings support grit's power to motivate and sustain family caregiving, in order for older adults to age in place as long as possible with finite resources. IMPLICATIONS FOR THE PROFESSION: This study highlights the importance of cultural awareness education for nurses, enabling continuity of care at a systems level and for a more resilient healthcare system. IMPACT: Family care partners' grit may be crucial for nurses to harness when together, they face limited access to culturally appropriate health and social services in a system grounded in values of equity and inclusion, as in Canada. REPORTING METHOD: When writing this manuscript, we adhered to relevant EQUATOR guidelines of the Consolidated Criteria for Reporting Qualitative Research (COREQ). PATIENT OR PUBLIC INVOLVEMENT AND ENGAGEMENT: No patient or public involvement.
Subject(s)
Asian People , Caregivers , Health Services Accessibility , Patient Acceptance of Health Care , Aged , Humans , Asian People/psychology , Canada/epidemiology , Caregivers/psychology , China/ethnology , Qualitative Research , Patient Acceptance of Health Care/ethnology , Patient Acceptance of Health Care/psychology , Intention , Ontario/epidemiology , Health Services Accessibility/statistics & numerical dataABSTRACT
In recent years, there have been significant advancements in Al-ion battery development, resulting in high voltage and capacity. Traditionally, only carbon-based materials with layered structures and strong bonding capabilities can deliver superior performance. However, most other materials exhibited low discharge voltages of 1.4 V, especially in aqueous Al-ion battery systems lacking anion intercalation. Thus, the development of high-voltage cathode materials has become crucial. This study introduces 2D MoS2 as a high-performance cathode for aqueous Al-ion batteries. The material's interlayer structure enables the intercalation of AlCl4 - anions, resulting in high-voltage intercalation. The resulting battery achieved a high voltage of 1.8 V with a capacity of 750 mAh g-1 , contributing to a high energy density of 890 Wh kg-1 and an impressive retention rate of ≈100% after 200 cycles. This research not only sheds light on the high-voltage anion-intercalation mechanism of MoS2 but also paves the way for the further development of advanced cathode materials in the field of Al-ion batteries. By demonstrating the potential of using 2D MoS2 as a cathode material, this finding can lead to the development of more efficient and innovative energy storage technologies, ultimately contributing to a sustainable and green energy future.
ABSTRACT
BACKGROUND: Although sleep disturbances and insomnia are common among Internally Displaced Persons (IDPs), these disorders remain largely understudied among victims fleeing ethnoreligious genocide. The Insomnia Severity Index (ISI), though a widely used measure of insomnia, has not been translated, cross-culturally adapted, nor validated in common African languages. This paper aimed to translate, adapt and validate the ISI scale into Hausa, the most widely spoken non-Indo-European language in African continent. METHODS: A six-stage validation model was used for the translation and adaptation of the ISI into Hausa [(ISI-Hausa), Item-Content Validity Index (I-CVI)=0.9 to 1.0]. The tool was administered among IDPs residing in Maiduguri, North-Eastern Nigeria, from October to November 2019. A total of 281 participants from six camps were recruited via convenience sampling. The psychometric properties of the scale were assessed using an Exploratory Factor Analysis (EFA), Cronbach's alpha (α) and Intraclass Correlation Coefficients (ICC) for determining factor structure, internal consistency and test-retest reliability, respectively. RESULTS: Exploratory factor reduction resulted in a two-factor solution, with " severity of insomnia " identified as the construct for Factor 1 and " impact of insomnia " as the construct for Factor 2. Factor 1 consisted of four scale items and Factor 2 consisted of three items. Factor loadings for each item ranged from 0.535-0.812. The scale demonstrated acceptable internal consistency (α=0.72) and good test-retest reliability (ICC=0.72) (p<0.001). CONCLUSION: The ISI-Hausa scale is a psychometrically sound and culturally relevant tool for assessing the severity and impact of insomnia among Hausa speaking IDPs in Africa.
Subject(s)
Refugees , Sleep Initiation and Maintenance Disorders , Cross-Cultural Comparison , Humans , Language , Nigeria , Psychometrics/methods , Reproducibility of Results , Sleep Initiation and Maintenance Disorders/diagnosis , Surveys and QuestionnairesABSTRACT
BACKGROUND: Smoking is an important modifiable risk factor of morbidities and mortality. Although healthcare professionals play an important role in smoking cessation, their adoption of such practices is relatively low because of inadequate training. To address this issue, we incorporated a service-learning model to operate the Youth Quitline. Undergraduate nursing students were trained and received supervision while delivering smoking cessation counseling through the Youth Quitline as their clinical placement. OBJECTIVES: We evaluated the effectiveness of the placement by assessing students' knowledge, attitudes and practices regarding smoking cessation and tobacco control. DESIGN: One-group pretest-posttest design. SETTING: Youth Quitline. PARTICIPANTS: A total of 61 third-year students in a mental health nursing program. METHODS: Students were required to complete 80 h at the Youth Quitline. The 80 h were divided into 20 sessions; students used four sessions to approach and recruit youth smokers in the community, then provided them with telephone counseling for the rest of the time. Prior to the placement, students attended a 2-day workshop. The outcomes were changes in students' knowledge, attitudes and practices regarding smoking cessation and tobacco control 3 months after the placement compared with baseline. RESULTS: From January-June 2021, students conducted 105 outreach activities to identify 3142 smokers in the community, and provided telephone counseling for 336 smokers via Youth Quitline. Compared with baseline, significant improvements were observed in students' knowledge, attitudes and practices regarding smoking cessation and tobacco control at 3-month follow-up. CONCLUSIONS: The clinical placement improved students' knowledge, attitudes and practices regarding smoking cessation and tobacco control, enhancing their competency in providing support to assist smokers to quit in their future practice. Incorporating the service-learning model in existing community-based services can provide additional venues for nursing students to practice. This is particularly important because many venues have restricted access during the COVID-19 pandemic.
Subject(s)
COVID-19 , Education, Nursing, Baccalaureate , Smoking Cessation , Students, Nursing , Adolescent , Counseling , Delivery of Health Care , Humans , Pandemics , Smoking Cessation/psychologyABSTRACT
Collection of skin very top layer, called stratum corneum, by tape stripping and the analysis of stratum corneum components by mass spectrometry provides multiple advantages for clinical studies that aim to understand the origins of allergic skin diseases and food allergy. However, such a methodology has multiple challenges on the way of complex stratum corneum analysis when molecules of different polarity are needed to be analyzed from minimal amount of skin tape strips. This review provides an overview of current knowledge about lipid and polar molecules in the skin, discusses challenging aspects of sample processing when dealing with skin tape strips, and provides some guidance towards approaches that generate complex, quantitative, normalized to total sample protein data that fit best the purpose of analysis of stratum corneum components for the purpose of clinical trials.
Subject(s)
EpidermisABSTRACT
BACKGROUND: Immunoglobulin E (IgE) blockade with omalizumab has demonstrated clinical benefit in pruritus-associated dermatoses (e.g. atopic dermatitis, bullous pemphigoid, urticaria). In oncology, pruritus-associated cutaneous adverse events (paCAEs) are frequent with immune checkpoint inhibitors (CPIs) and targeted anti-human epidermal growth factor receptor 2 (HER2) therapies. Thus, we sought to evaluate the efficacy and safety of IgE blockade with omalizumab in cancer patients with refractory paCAEs related to CPIs and anti-HER2 agents. PATIENTS AND METHODS: Patients included in this multicenter retrospective analysis received monthly subcutaneous injections of omalizumab for CPI or anti-HER2 therapy-related grade 2/3 pruritus that was refractory to topical corticosteroids plus at least one additional systemic intervention. To assess clinical response to omalizumab, we used the Common Terminology Criteria for Adverse Events version 5.0. The primary endpoint was defined as reduction in the severity of paCAEs to grade 1/0. RESULTS: A total of 34 patients (50% female, median age 67.5 years) received omalizumab for cancer therapy-related paCAEs (71% CPIs; 29% anti-HER2). All had solid tumors (29% breast, 29% genitourinary, 15% lung, 26% other), and most (n = 18, 64%) presented with an urticarial phenotype. In total 28 of 34 (82%) patients responded to omalizumab. The proportion of patients receiving oral corticosteroids as supportive treatment for management of paCAEs decreased with IgE blockade, from 50% to 9% (P < 0.001). Ten of 32 (31%) patients had interruption of oncologic therapy due to skin toxicity; four of six (67%) were successfully rechallenged following omalizumab. There were no reports of anaphylaxis or hypersensitivity reactions related to omalizumab. CONCLUSIONS: IgE blockade with omalizumab demonstrated clinical efficacy and was well tolerated in cancer patients with pruritus related to CPIs and anti-HER2 therapies.
Subject(s)
Immunoglobulin E , Omalizumab , Aged , Female , Humans , Immune Checkpoint Inhibitors , Male , Omalizumab/adverse effects , Pruritus/chemically induced , Pruritus/drug therapy , Retrospective StudiesABSTRACT
The global coronavirus disease (COVID-19) pandemic poses an unprecedented stress on healthcare systems internationally. These Health system-wide demands call for efficient utilisation of resources at this time in a fair, consistent, ethical and efficient manner would improve our ability to treat patients. Excellent co-operation between hospital units (especially intensive care unit [ICU], emergency department [ED] and cardiology) is critical in ensuring optimal patient outcomes. The purpose of this document is to provide practical guidelines for the effective use of interventional cardiology services in Australia and New Zealand. The document will be updated regularly as new evidence and knowledge is gained with time. Goals Considerations.
Subject(s)
Betacoronavirus , Consensus , Coronavirus Infections , Critical Care , Intensive Care Units , Pandemics , Pneumonia, Viral , Australia/epidemiology , COVID-19 , Cardiology/standards , Coronavirus Infections/epidemiology , Coronavirus Infections/physiopathology , Coronavirus Infections/therapy , Humans , New Zealand/epidemiology , Pneumonia, Viral/epidemiology , Pneumonia, Viral/physiopathology , Pneumonia, Viral/therapy , Practice Guidelines as Topic , SARS-CoV-2ABSTRACT
BACKGROUND: Gut microbiota may play a role in egg allergy. We sought to examine the association between early-life gut microbiota and egg allergy. METHODS: We studied 141 children with egg allergy and controls from the multicenter Consortium of Food Allergy Research study. At enrollment (age 3 to 16 months), fecal samples were collected, and clinical evaluation, egg-specific IgE measurement, and egg skin prick test were performed. Gut microbiome was profiled by 16S rRNA sequencing. Analyses for the primary outcome of egg allergy at enrollment, and the secondary outcomes of egg sensitization at enrollment and resolution of egg allergy by age 8 years, were performed using Quantitative Insights into Microbial Ecology, Phylogenetic Investigation of Communities by Reconstruction of Unobserved States, and Statistical Analysis of Metagenomic Profiles. RESULTS: Compared to controls, increased alpha diversity and distinct taxa (PERMANOVA P = 5.0 × 10-4 ) characterized the early-life gut microbiome of children with egg allergy. Genera from the Lachnospiraceae, Streptococcaceae, and Leuconostocaceae families were differentially abundant in children with egg allergy. Predicted metagenome functional analyses showed differential purine metabolism by the gut microbiota of egg-allergic subjects (Kruskal-Wallis Padj = 0.021). Greater gut microbiome diversity and genera from Lachnospiraceae and Ruminococcaceae were associated with egg sensitization (PERMANOVA P = 5.0 × 10-4 ). Among those with egg allergy, there was no association between early-life gut microbiota and egg allergy resolution by age 8 years. CONCLUSION: The distinct early-life gut microbiota in egg-allergic and egg-sensitized children identified by our study may point to targets for preventive or therapeutic intervention.
Subject(s)
Egg Hypersensitivity/etiology , Gastrointestinal Microbiome , Age Factors , Case-Control Studies , Female , Gastrointestinal Microbiome/immunology , Humans , Immunization , Immunoglobulin E/immunology , Infant , Male , Metagenome , Metagenomics , RNA, Ribosomal, 16SABSTRACT
Mechanisms driving acute food allergic reactions have not been fully characterized. We profile the dynamic transcriptome of acute peanut allergic reactions using serial peripheral blood samples obtained from 19 children before, during, and after randomized, double-blind, placebo-controlled oral challenges to peanut. We identify genes with changes in expression triggered by peanut, but not placebo, during acute peanut allergic reactions. Network analysis reveals that these genes comprise coexpression networks for acute-phase response and pro-inflammatory processes. Key driver analysis identifies six genes (LTB4R, PADI4, IL1R2, PPP1R3D, KLHL2, and ECHDC3) predicted to causally modulate the state of coregulated networks in response to peanut. Leukocyte deconvolution analysis identifies changes in neutrophil, naive CD4+ T cell, and macrophage populations during peanut challenge. Analyses in 21 additional peanut allergic subjects replicate major findings. These results highlight key genes, biological processes, and cell types that can be targeted for mechanistic study and therapeutic targeting of peanut allergy.
Subject(s)
Acute-Phase Reaction/genetics , Peanut Hypersensitivity/genetics , RNA, Messenger/metabolism , Acute-Phase Reaction/immunology , Adolescent , CD4-Positive T-Lymphocytes/immunology , Child , Double-Blind Method , Enoyl-CoA Hydratase/genetics , Female , Gene Expression Profiling , Gene Regulatory Networks , Humans , Inflammation/genetics , Inflammation/immunology , Macrophages/immunology , Male , Microfilament Proteins/genetics , Nerve Tissue Proteins/genetics , Neutrophils/immunology , Peanut Hypersensitivity/immunology , Protein Phosphatase 1/genetics , Protein-Arginine Deiminase Type 4 , Protein-Arginine Deiminases/genetics , Random Allocation , Receptors, Interleukin-1 Type II/genetics , Receptors, Leukotriene B4/genetics , Reproducibility of ResultsABSTRACT
BACKGROUND: In a previously reported CoFAR study, 55 subjects with egg allergy underwent randomized, placebo-controlled egg oral immunotherapy (eOIT). Active treatment induced desensitization in most and sustained unresponsiveness (SU) in a smaller subset. We hypothesized that component-resolved analysis of IgE, IgG4, IgA, IgA1, and IgA2 may identify potential biomarkers of SU in OIT subjects. METHODS: Longitudinal samples for 51 egg-allergic subjects (37 active and 14 placebo) were available. Egg white (EW)-, ovalbumin (OVA)-, and ovomucoid (OVM)-specific levels of IgA, IgA1, and IgA2 were quantified by ELISA. IgE and IgG4 to these antigens were quantified using ImmunoCAP® . Clinical responders achieved SU to egg; all others were considered nonresponders. Between-group comparisons were made among active and placebo, as well as responders and nonresponders. RESULTS: No placebo subjects achieved responder status. Through month 48, among the 37 active subjects, baseline IgE-OVM was lower in responders (median 3.97 kU/l, n = 19) than in nonresponders (10.9 kU/l, n = 18, P = 0.010). Logistic regression analysis revealed that lower baseline IgE-EW (P = 0.038), IgE-OVM (P = 0.032), and a higher IgG4/IgE-OVM ratio (P = 0.013) were associated with clinical response. Relative increases in IgG4-EW, IgA-EW, and IgA2-EW were observed in responders (P = 0.024, 0.024, and 0.029, respectively). IgG4/IgE, IgA/IgE, and IgA2/IgE ratios for EW and IgA/IgE ratio for OVA were found to be significantly elevated among responders (P = 0.004, 0.009, 0.028, and 0.008, respectively). CONCLUSIONS: Increased IgG4-EW, IgA-EW, and IgA2-EW during eOIT are associated with clinical response to eOIT. Lower pretreatment IgE-EW and IgE-OVM are also associated with SU. Future studies are needed to evaluate and validate these potential biomarkers.
Subject(s)
Allergens/immunology , Desensitization, Immunologic , Egg Hypersensitivity/immunology , Egg Hypersensitivity/therapy , Eggs/adverse effects , Immunoglobulin A/immunology , Immunoglobulin E/immunology , Immunoglobulin G/immunology , Administration, Oral , Allergens/administration & dosage , Biomarkers , Desensitization, Immunologic/methods , Female , Humans , Immunoglobulin A/blood , Immunoglobulin E/blood , Immunoglobulin G/blood , Male , Treatment Failure , Treatment OutcomeABSTRACT
OBJECTIVE: To examine if there were changes in the proportion of hardcore smokers and factors associated with hardcore smoking before and after implementation of smoke-free legislation, and warning labels on cigarette packets in Hong Kong in January 2007. STUDY DESIGN: Repeated cross-sectional surveys of the general population in Hong Kong. METHODS: Data from all daily smokers aged ≥ 15 years in the population-based Thematic Household Surveys from 2005 (n = 3740) and 2008 (n = 2958) were used to estimate the prevalence of hardcore smokers before and after implementation of smoke-free legislation. A logistic regression model was used to identify the factors associated with hardcore smoking, and to examine if there were any changes in their associations with the likelihood of hardcore smoking after implementation of smoke-free legislation. RESULTS: The proportion of hardcore smokers among current daily smokers increased significantly from 22.5% [95% confidence interval (CI) 21.1-23.8%] in 2005 to 28.3% (95% CI 26.7-29.9%) in 2008. Change in the strength of the association of hardcore smoking with three factors was observed. The strength of the association between hardcore smoking and 'necessity in social functions' [odds ratio (OR) 0.54, 95% CI 0.31-0.95) and 'necessity for killing time' (OR 0.56, 95% CI 0.36-0.89) decreased, while the association between hardcore smoking and 'necessity as refreshment' increased (OR 3.02, 95% CI 1.43-6.39) after implementation of smoke-free legislation and warning labels on cigarette packets. 'Smoking had become a habit' was the factor associated most strongly with hardcore smoking (OR 4.88, 95% CI 4.02-5.93). CONCLUSIONS: The proportion of hardcore smokers remained stable in Hong Kong from 2005 to 2008. While the implementation of the two tobacco control measures may have provided an environment to reduce social smoking in hardcore smokers, addiction appeared to be the most important factor associated with hardcore smoking. More effective and tailor-made cessation services that target this group of smokers are needed.
Subject(s)
Product Labeling/legislation & jurisprudence , Smoking/legislation & jurisprudence , Smoking/psychology , Tobacco Smoke Pollution/legislation & jurisprudence , Adolescent , Adult , Cross-Sectional Studies , Female , Health Surveys , Hong Kong/epidemiology , Humans , Logistic Models , Male , Middle Aged , Risk Factors , Smoking/epidemiology , Tobacco Smoke Pollution/prevention & control , Young AdultABSTRACT
BACKGROUND: Subjects with atopic dermatitis (AD) have defects in antimicrobial peptide (AMP) production possibly contributing to an increased risk of infections. In laboratory models, vitamin D can alter innate immunity by increasing AMP production. OBJECTIVE: To determine if AD severity correlates with baseline vitamin D levels, and to test whether supplementation with oral vitamin D alters AMP production in AD skin. METHODS: This was a multi-centre, placebo-controlled, double-blind study in 30 subjects with AD, 30 non-atopic subjects, and 16 subjects with psoriasis. Subjects were randomized to receive either 4000 IU of cholecalciferol or placebo for 21 days. At baseline and day 21, levels of 25-hydroxyvitamin D (25OHD), cathelicidin, HBD-3, IL-13, and Eczema Area and Severity Index (EASI) and Rajka-Langeland scores were obtained. RESULTS: At baseline, 20% of AD subjects had serum 25OHD below 20 ng/mL. Low serum 25OHD correlated with increased Fitzpatrick Skin Type and elevated BMI, but not AD severity. After 21 days of oral cholecalciferol, mean serum 25OHD increased, but there was no significant change in skin cathelicidin, HBD-3, IL-13 or EASI scores. CONCLUSIONS: This study illustrated that darker skin types and elevated BMI are important risk factors for vitamin D deficiency in subjects with AD, and highlighted the possibility that seasonality and locale may be potent contributors to cathelicidin induction through their effect on steady state 25OHD levels. Given the molecular links between vitamin D and immune function, further study of vitamin D supplementation in subjects with AD is warranted.
Subject(s)
Cholecalciferol/therapeutic use , Dermatitis, Atopic/drug therapy , Dietary Supplements , Vitamins/therapeutic use , Adult , Dermatitis, Atopic/blood , Double-Blind Method , Female , Humans , Male , Severity of Illness Index , Vitamin D/analogs & derivatives , Vitamin D/bloodABSTRACT
BACKGROUND: The role of CD8 T lymphocytes in the pathogenesis of asthma is not well understood. We investigated whether a subset of IL-13-producing BLT1-positive CD8 T lymphocytes are present in asthmatic airways and are associated with impaired lung function. METHODS: Bronchoalveolar lavage (BAL) cells were obtained from asthmatic (n = 39) and healthy control (n = 28) subjects. Cells were stimulated with phorbol ester and ionomycin in the presence of brefeldin A and stained for CD8, BLT1, and intracellular IL-13. The frequency of IL-13-producing BLT1-positive CD8 T lymphocytes was compared between the two groups and related to lung function, serum IgE levels, and reticular basement membrane (RBM) thickness. RESULTS: A subset of CD8 T lymphocytes expressing BLT1 and producing IL-13 were detected in the airways of all asthmatic subjects. The frequency of this subset among recovered lymphocytes was significantly higher in the airways of asthmatic subjects compared with controls (mean ± SEM: 16.2 ± 1.4 vs 5.3 ± 0.5, respectively, P < 0.001) and correlated positively with serum IgE levels and RBM thickness. More importantly, the frequency of CD8 T lymphocytes co-expressing BLT1 and IL-13 was inversely related to FEV1 and FEF[25-75] percent predicted values (P < 0.001). CONCLUSIONS: A subset of CD8 T lymphocytes expressing BLT1 and producing IL-13 is present in the airways of asthmatics. The accumulation of these cells is associated with airway obstruction, suggesting that they may play a significant pathogenic role in bronchial asthma.
Subject(s)
Airway Obstruction/immunology , Airway Obstruction/metabolism , Asthma/immunology , Asthma/metabolism , CD8-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/metabolism , Interleukin-13/biosynthesis , Receptors, Leukotriene B4/metabolism , Adolescent , Adult , Asthma/physiopathology , Bronchoalveolar Lavage Fluid/cytology , Bronchoalveolar Lavage Fluid/immunology , Case-Control Studies , Female , Humans , Male , Middle Aged , Respiratory Function Tests , Young AdultABSTRACT
BACKGROUND: The increased susceptibility of patients with atopic dermatitis (AD) to disseminated viral skin infections such as eczema herpeticum (ADEH+) is poorly understood. OBJECTIVES: The primary goal of the current study was to determine whether ADEH+ subjects have identifiable defects in cell-mediated immunity that reduce their ability to control viral infections. MATERIALS AND METHODS: In this study, we evaluated cytokine expression by various subsets of peripheral blood mononuclear cells from ADEH+ (n = 24) compared with AD without a history of viral infections (ADEH-) (n = 20) before and after treatment with herpes simplex virus (HSV). RESULTS: We found that interferon (IFN)-γ expression after HSV treatment was lower in the CD8+ T cells and monocytes from patients with ADEH+ compared with patients who are ADEH- or nonatopic. Given the induction of CD8+ T cells as the result of antigen presentation by human leucocyte antigen (HLA) class I, consistent with the findings described above we also found that the HLA B7 allele was significantly associated with risk of the ADEH+ phenotype (odds ratio = 1·91, P = 0·02, 125 ADEH+ and 161 ADEH- subjects). CONCLUSIONS: These data suggest that defects in viral-induced IFN-γ from CD8+ T cells contribute to the ADEH+ phenotype.
Subject(s)
CD8-Positive T-Lymphocytes/immunology , Dermatitis, Atopic/immunology , HLA-B7 Antigen/immunology , Immunity, Cellular/physiology , Interferon-gamma/biosynthesis , Kaposi Varicelliform Eruption/immunology , CD8-Positive T-Lymphocytes/metabolism , Case-Control Studies , Dermatitis, Atopic/complications , Gene Frequency , HLA-B7 Antigen/genetics , Humans , Kaposi Varicelliform Eruption/complications , Leukocytes, Mononuclear/immunology , PhenotypeABSTRACT
BACKGROUND: Glucocorticoid-induced TNF receptor-related protein ligand (GITRL), a ligand for the T cell co-stimulatory molecule GITR, is expressed by keratinocytes and involved in chemokine production. The expression of GITRL in skin inflammation remains unknown. OBJECTIVES: This study investigated cytokine regulation of keratinocyte GITRL expression. METHODS: Glucocorticoid-induced TNF receptor expression was evaluated in cytokine-treated human epidermal keratinocytes (HEK)s, murine PAM 212 cell line, murine and human skin explants by real time PCR, flow cytometry and immunostaining. Functional responses to GITR fusion protein were examined by real time PCR and ELISA. GITRL expression in AD and psoriasis was studied by immunohistochemistry. RESULTS: Skin biopsies from STAT6VT transgenic mice, which develop spontaneous atopic skin inflammation, were found by immunofluoresence, to have increased keratinocyte GITRL expression. Exposure to Th2 cytokines augmented GITRL mRNA expression in the murine PAM 212 keratinocytic cell line and murine skin explants. In contrast, GITRL mRNA and protein expression was only increased in HEKs and human skin explants in the presence of the combination of TNF-α and Th2 cytokines. A synergistic effect of Th2 cytokines and GITR fusion protein on production of CCL17, the Th2 chemokine, by murine keratinocytes was demonstrated. Immunohistochemical staining showed that acute AD lesions have increased expression of GITRL compared with normal skin, chronic AD lesions and psoriatic plaques. CONCLUSIONS AND CLINICAL RELEVANCE: Our studies demonstrate that GITRL expression is augmented by Th2 cytokines and TNF-α in keratinocytes. Increased GITRL expression in acute AD skin lesions is shown. This observation suggests a link between cytokine-regulated keratinocyte GITRL expression and its role in inflammatory responses in AD.