Immune profiling reveals umbilical cord blood mononuclear cells from South India display an IL-8 dominant, CXCL-10 deficient polyfunctional monocyte response to pathogen-associated molecular patterns that is distinct from adult blood cells.

Neonate responses to pathogen-associated molecular patterns (PAMPS) differ from adults; such understanding is poor in Indian neonates, despite recognized significant infectious risk. Immune profiling analysis was undertaken of 10 secreted mediators contextualized with cellular source induced by six PAMPs in umbilical cord (CB; n = 21) and adult-blood (PBMC; n = 14) from a tertiary care hospital in South India. Differential cytokine expression analysis (minimum log2-fold difference; adj P-value < 0.

Vitamin D3 regulates PM-driven primary human neutrophil inflammatory responses.

Recent evidence has demonstrated that both acute and chronic exposure to particulate air pollution are risk factors for respiratory tract infections and increased mortality from sepsis. There is therefore an urgent need to establish the impact of ambient particulate matter (PM) on innate immune cells and to establish potential strategies to mitigate against adverse effects. PM has previously been reported to have potential adverse effects on neutrophil function.

The Induction of Alpha-1 Antitrypsin by Vitamin D in Human T Cells Is TGF-β Dependent: A Proposed Anti-inflammatory Role in Airway Disease.

Vitamin D upregulates anti-inflammatory and antimicrobial pathways that promote respiratory health. Vitamin D synthesis is initiated following skin exposure to sunlight, however nutritional supplementation can be required to address deficiency, for example during the winter months or due to cultural constraints. We recently reported that 1α,25-dihydroxyvitamin D3 (1,25(OH)D3) treatment induced alpha-1 antitrypsin (AAT) expression in CD4+, but not CD8+ T cells, with evidence supporting an immunoregulatory role.

Menopausal hormone therapy and women's health: An umbrella review.

Background: There remains uncertainty about the impact of menopausal hormone therapy (MHT) on women's health. A systematic, comprehensive assessment of the effects on multiple outcomes is lacking. We conducted an umbrella review to comprehensively summarize evidence on the benefits and harms of MHT across diverse health outcomes.

Hormone Replacement Therapy and Risk of Severe Asthma Exacerbation in Perimenopausal and Postmenopausal Women: 17-Year National Cohort Study.

Background: The impact of hormone replacement therapy (HRT) on clinical outcomes in menopausal women is uncertain.

Objective: To investigate the association between use of HRT and severe asthma exacerbation in perimenopausal and postmenopausal women with asthma.

Methods: We used the Optimum Patient Care Research Database, a population-based longitudinal primary care database in the United Kingdom, to construct a 17-year (January 1, 2000, to December 31, 2016) cohort of perimenopausal and postmenopausal (46-70 years, N = 31,656) women.

Hormone replacement therapy and asthma onset in menopausal women: National cohort study.

Background: There is uncertainty about the role of hormonal replacement therapy (HRT) in the development of asthma.

Objective: We investigated whether use of HRT and duration of use was associated with risk of development of asthma in perimenopausal and postmenopausal women.

Methods: We constructed a 17-year (from January 1, 2000, to December 31, 2016) open cohort of 353,173 women (aged 46-70 years) from the Optimum Patient Care Database, a longitudinal primary care database from across the United Kingdom.

Hormonal contraception and the risk of severe asthma exacerbation: 17-year population-based cohort study.

Background: Longitudinal studies investigating impact of exogenous sex steroids on clinical outcomes of asthma in women are lacking. We investigated the association between use of hormonal contraceptives and risk of severe asthma exacerbation in reproductive-age women with asthma.

Methods: We used the Optimum Patient Care Research Database, a population-based, longitudinal, anonymised primary care database in the UK, to construct a 17-year (1 January 2000-31 December 2016) retrospective cohort of reproductive-age (16-45 years, n=83 084) women with asthma.

Allergens TRP a swITCH to Initiate Type 2 Immunity.

Allergens induce type-2 immunity, but unresolved questions remain about initiation of this response. In this issue, Perner et al. propose that cutaneous activation of TRPV1 sensory neurons by protease allergens stimulates release of substance P to induce migration of Th2-skewing CD301b DC to draining lymph nodes.

WITHDRAWN: Allergic mechanisms of asthma are enhanced during the summer with oxidant PM components.

This article has been withdrawn at the request of the author(s) and/or editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at https://www.

The Hidden Burden of Severe Asthma: From Patient Perspective to New Opportunities for Clinicians.

Severe asthma is an important topic in respiratory diseases, due to its high impact on morbidity and mortality as well as on health-care resources. The many challenges that still exist in the management of the most difficult-to-treat forms of the disease, and the acknowledgement of the existence of unexplored areas in the pathophysiological mechanisms and the therapeutic targets represent an opportunity to gather experts in the field with the immediate goals to summarize current understanding about the natural history of severe asthma and to identify gaps in knowledge and research opportunities, with the aim to contribute to improved medical care and health outcomes. This article is a consensus document from the "International Course on Severe Asthma" that took place in Palermo, Italy, on May 10-11, 2019.

Effects of vitamin D supplementation on circulating concentrations of growth factors and immune-mediators in healthy women during pregnancy.

Background: For the second aim of the Kellogg Foundation grant, this double-blind RCT investigated the impact of plasma vitamin D metabolite 25-hydroxyvitamin D (25(OH)D) on plasma immune-mediators during pregnancy. We hypothesized that higher 25(OH)D concentrations would associate with reduced pro-inflammatory and increased tolerogenic immune-mediator concentrations.

Methods: Pregnant women enrolled at 10-14 weeks gestation were randomized to 400 or 4400 IU vitamin D/day.

Hormonal contraceptives and onset of asthma in reproductive-age women: Population-based cohort study.

Background: Despite well-described sex differences in asthma incidence, there remains uncertainty about the role of female sex hormones in the development of asthma.

Objective: We sought to investigate whether hormonal contraceptive use, its subtypes, and duration of use were associated with new-onset asthma in reproductive-age women.

Methods: Using the Optimum Patient Care Research Database, a UK national primary care database, we constructed an open cohort of 16- to 45-year-old women (N = 564,896) followed for up to 17 years (ie, January 1, 2000, to December 31, 2016).

Air pollution and its effects on the immune system.

A well-functioning immune system is vital for a healthy body. Inadequate and excessive immune responses underlie diverse pathologies such as serious infections, metastatic malignancies and auto-immune conditions. Therefore, understanding the effects of ambient pollutants on the immune system is vital to understanding how pollution causes disease, and how that pathology could be abrogated.

Vitamin D: can the sun stop the atopic epidemic?

Purpose Of Review: To review recent evidence on the capacity of vitamin D to prevent atopic disease, focussing on food allergy and asthma, and potential underlying mechanisms.

Recent Findings: The incidence of allergic disease continues to increase worldwide. Vitamin D status is influenced by sun exposure and dietary intake.

Vitamin D (1,25(OH)D3) induces α-1-antitrypsin synthesis by CD4 T cells, which is required for 1,25(OH)D3-driven IL-10.

Studies to identify novel immune-regulatory functions of active vitamin D (1,25(OH)D3) in human CD4 T cells revealed that 1,25(OH)D3 potently induced expression of the gene SERPINA1, encoding the anti-protease α-1-antitrypsin. We confirmed α-1-antitrypsin protein expression by 1,25(OH)D3-treated CD4 T cells, but not in CD8 T cells or monocytes. α-1-Antitrypsin promotes anti-inflammatory IL-10 synthesis in other immune cell populations.

High-Dose IL-2 Skews a Glucocorticoid-Driven IL-17IL-10 Memory CD4 T Cell Response towards a Single IL-10-Producing Phenotype.

Glucocorticoids are known to increase production of the anti-inflammatory cytokine IL-10, and this action is associated with their clinical efficacy in asthmatics. However, glucocorticoids also enhance the synthesis of IL-17A by PBMCs, which, in excess, is associated with increased asthma severity and glucocorticoid-refractory disease. In this study, we show that the glucocorticoid dexamethasone significantly increased IL-10 production by human memory CD4 T cells from healthy donors, as assessed by intracellular cytokine staining.

Effects of vitamin D on inflammatory and oxidative stress responses of human bronchial epithelial cells exposed to particulate matter.

Background: Particulate matter (PM) pollutant exposure, which induces oxidative stress and inflammation, and vitamin D insufficiency, which compromises immune regulation, are detrimental in asthma.

Objectives: Mechanistic cell culture experiments were undertaken to ascertain whether vitamin D abrogates PM-induced inflammatory responses of human bronchial epithelial cells (HBECs) through enhancement of antioxidant pathways.

Methods: Transcriptome analysis, PCR and ELISA were undertaken to delineate markers of inflammation and oxidative stress; with comparison of expression in primary HBECs from healthy and asthmatic donors cultured with reference urban PM in the presence/absence of vitamin D.

Exogenous sex steroid hormones and asthma in females: protocol for a population-based retrospective cohort study using a UK primary care database.

Introduction: Female sex steroid hormones have been implicated in sex-related differences in the development and clinical outcomes of asthma. The role of exogenous sex steroids, however, remains unclear. Our recent systematic review highlighted the lack of high-quality population-based studies investigating this subject.

Urban particulate matter stimulation of human dendritic cells enhances priming of naive CD8 T lymphocytes.

Epidemiological studies have consistently shown associations between elevated concentrations of urban particulate matter (UPM) air pollution and exacerbations of asthma and chronic obstructive pulmonary disease, which are both associated with viral respiratory infections. The effects of UPM on dendritic cell (DC) -stimulated CD4 T lymphocytes have been investigated previously, but little work has focused on CD8 T-lymphocyte responses despite their importance in anti-viral immunity. To address this, we examined the effects of UPM on DC-stimulated naive CD8 T-cell responses.

Vitamin D in Asthma: Mechanisms of Action and Considerations for Clinical Trials.

There is increasing interest in the therapeutic utility of vitamin D in asthma, which is supported by a significant body of evidence on epidemiologic associations between vitamin D insufficiency and worse asthma control. In support of a causal relationship, vitamin D beneficially modulates diverse immunologic pathways in heterogeneous asthma endotypes, regulating the actions of lymphocytes, mast cells, antigen-presenting cells, and structural cells to dampen excessive inflammatory responses. Allergic asthma is characterized by a failure of immune tolerance and the development of pathologic responses to inhaled aeroallergens, and vitamin D has been extensively shown to support immune regulation.

Vitamin D supplementation during pregnancy: Effect on the neonatal immune system in a randomized controlled trial.

Background: Programming of the immune system during fetal development can influence asthma-related risk factors and outcomes in later life. Vitamin D is a well-recognized immune modulator, and deficiency of this nutrient during pregnancy is hypothesized to influence disease development in offspring.

Objective: We sought to investigate the effect on neonatal immunity of maternal supplementation with 4400 IU/d vitamin D during the second and third trimesters of pregnancy by using a subset of cord blood samples from a randomized, double-blind, placebo-controlled clinical trial (the Vitamin D Antenatal Asthma Reduction Trial).

Vitamin D Counteracts an IL-23-Dependent IL-17AIFN-γ Response Driven by Urban Particulate Matter.

Urban particulate matter (UPM) air pollution and vitamin D deficiency are detrimentally associated with respiratory health. This is hypothesized to be due in part to regulation of IL-17A, which UPM is reported to promote. Here, we used a myeloid dendritic cell (DC)-memory CD4 T cell co-culture system to characterize UPM-driven IL-17A cells, investigate the mechanism by which UPM-primed DCs promote this phenotype, and address evidence for cross-regulation by vitamin D.

Addressing unmet needs in understanding asthma mechanisms: From the European Asthma Research and Innovation Partnership (EARIP) Work Package (WP)2 collaborators.

Asthma is a heterogeneous, complex disease with clinical phenotypes that incorporate persistent symptoms and acute exacerbations. It affects many millions of Europeans throughout their education and working lives and puts a heavy cost on European productivity. There is a wide spectrum of disease severity and control.

Activin-A co-opts IRF4 and AhR signaling to induce human regulatory T cells that restrain asthmatic responses.

Type 1 regulatory T (Tr1) cells play a pivotal role in restraining human T-cell responses toward environmental allergens and protecting against allergic diseases. Still, the precise molecular cues that underlie their transcriptional and functional specification remain elusive. Here, we show that the cytokine activin-A instructs the generation of CD4 T cells that express the Tr1-cell-associated molecules IL-10, inducible T-Cell costimulator (ICOS), lymphocyte activation gene 3 protein (LAG-3), and CD49b, and exert strongly suppressive functions toward allergic responses induced by naive and in vivo-primed human T helper 2 cells.