Professor Prue Hart

Epstein–Barr virus infection, B-cell dysfunction and other risk factors converge in gut-associated lymphoid tissue to drive the immunopathogenesis of multiple sclerosis: a hypothesis

Multiple sclerosis is associated with Epstein–Barr virus (EBV) infection, B-cell dysfunction, gut dysbiosis, and environmental and genetic risk factors, including female sex.

Developing an Online Tool to Promote Safe Sun Behaviors With Young Teenagers as Co-researchers

Despite education about the risks of excessive sun exposure, teenagers in Australia are sun-seeking, with sunburn common in summer. Conversely, some regular (time-limited) exposure to sunlight (that avoids sunburn) is necessary for vitamin D and healthy bones and other molecules important for immune and metabolic health. New interventions are thus required to better support teenagers to make healthy and balanced decisions about their sun behaviors.

Circulating Memory B Cells in Early Multiple Sclerosis Exhibit Increased IgA+ Cells, Globally Decreased BAFF-R Expression and an EBV-Related IgM+ Cell Signature

Multiple sclerosis (MS) is an immune-mediated inflammatory disease of the central nervous system that results in demyelination of axons, inefficient signal transmission and reduced muscular mobility. Recent findings suggest that B cells play a significant role in disease development and pathology. To further explore this, B cell profiles in peripheral blood from 28 treatment-naive patients with early MS were assessed using flow cytometry and compared to 17 healthy controls.

Sex-Specific Environmental Impacts on Initiation and Progression of Multiple Sclerosis

The immunological mechanisms that contribute to multiple sclerosis (MS) differ between males and females. Females are 2-3 times more likely to develop MS compared to males, however the reason for this discrepancy is unknown. Once MS is established, there is a more inflammatory yet milder form of disease in females whereas males generally suffer from more severe disease and faster progression, neural degradation, and disability.

Changes in serum neurofilament light chain levels following narrowband ultraviolet B phototherapy in clinically isolated syndrome

To determine whether serum neurofilament light chain (sNfL) levels are suppressed in patients with the clinically isolated syndrome (CIS) following narrowband ultraviolet B phototherapy (UVB-PT).

Higher ultraviolet radiation during early life is associated with lower risk of childhood type 1 diabetes among boys

Population-level ecological studies show type 1 diabetes incidence is inversely correlated with ambient ultraviolet radiation (UVR) levels. We conducted a nested case–control study using administrative datasets to test this association at the individual level.

Demographic and clinical predictors of vitamin D status in pregnant women tested for deficiency in Western Australia

This study aimed to describe the vitamin D status of pregnant women in Western Australia and identify predictors of deficiency in pregnancy. A cross-sectional study was conducted using linked data from statewide administrative data collections.

More Than Effects in Skin: Ultraviolet Radiation-Induced Changes in Immune Cells in Human Blood

Cells of the skin and circulation are in constant two-way communication. Following exposure of humans to sunlight or to phototherapy, there are alterations in the number, phenotype and function of circulating blood cells.

Expression of CYP24A1 and other multiple sclerosis risk genes in peripheral blood indicates response to vitamin D in homeostatic and inflammatory conditions

Although genetic and epidemiological evidence indicates vitamin D insufficiency contributes to multiple sclerosis (MS), and serum levels of vitamin D increase on treatment with cholecalciferol, recent metanalyses indicate that this vitamin D form does not ameliorate disease. Genetic variation in genes regulating vitamin D, and regulated by vitamin D, affect MS risk.

Metabolic dysfunction induced by a high-fat diet modulates hematopoietic stem and myeloid progenitor cells in brown adipose tissue of mice

Brown adipose tissue (BAT) may be an important metabolic regulator of whole-body glucose. While important roles have been ascribed to macrophages in regulating metabolic functions in BAT, little is known of the roles of other immune cells subsets, particularly dendritic cells (DCs). Eating a high-fat diet may compromise the development of hematopoietic stem and progenitor cells (HSPCs)-which give rise to DCs-in bone marrow, with less known of its effects in BAT. We have previously demonstrated that ongoing exposure to low-dose ultraviolet radiation (UVR) significantly reduced the 'whitening' effect of eating a high-fat diet upon interscapular (i) BAT of mice.

Use of linked administrative and laboratory data to confirm that serum 25(OH)D levels in pregnant women can be predicted from satellite estimates of ultraviolet radiation

Serum 25 hydroxyvitamin D [25(OH)D] levels of pregnant women have been linked to various health outcomes in their offspring. Satellite-derived ultraviolet radiation (UVR) data have been used as a proxy for 25(OH)D levels, as individual-level cohort studies are time-consuming, costly and only feasible for common outcomes.

FcgammaRIIb Expression Is Decreased on Naive and Marginal Zone-Like B Cells From Females With Multiple Sclerosis

B cells are critical to the development of multiple sclerosis (MS), but the mechanisms by which they contribute to the disease are poorly defined. We hypothesised that the expression of CD32b (FcγRIIb), a receptor for the Fc region of IgG with inhibitory activities in B cells, is lower on B cell subsets from people with clinically isolated syndrome (CIS) or MS. CD32b expression was highest on post-naive IgM+ B cell subsets in healthy controls. For females with MS or CIS, significantly lower CD32b expression was identified on IgM+ B cell subsets, including naive and IgMhi MZ-like B cells, when compared with control females. Lower CD32b expression on these B cell subsets was associated with detectable anti-Epstein Barr Virus viral capsid antigen IgM antibodies, and higher serum levels of B cell activating factor. To investigate the effects of lower CD32b expression, B cells were polyclonally activated in the presence of IgG immune complexes, with or without a CD32b blocking antibody, and the expression of TNF and IL-10 in B cell subsets was assessed.

Narrowband UVB phototherapy reduces TNF production by B-cell subsets stimulated via TLR7 from individuals with early multiple sclerosis

At the end of a 60-day course of narrowband UVB phototherapy, administered to individuals with early multiple sclerosis, there were changes in the relative proportions of circulating B-cell subsets. This study investigated phototherapy-associated changes to cytokine responses of B cells when exposed to a TLR7 ligand.

IgG3 + B cells are associated with the development of multiple sclerosis

We have identified previously uncharacterised subsets of IgG3 + B cells and shown them to correlate with autoimmune attacks on the central nervous system

Low-dose UV radiation before running wheel access activates brown adipose tissue

When combined with physical activity, low-dose UVR may more effectively limit adiposity and modulate metabolic and immune pathways in iBAT

Are there differences in immune responses following delivery of vaccines through acutely or chronically sun-exposed compared with sun-unexposed skin?

The review provides the basis for further research into the effects of acute and chronic UV radiation exposure on skin cells in the context of vaccination

Effects of UVR exposure on the gut microbiota of mice and humans

Both human and murine studies report that multiple exposures to sub-erythemal UV radiation can increase the diversity of the gut microbiome

Characterising nitric oxide-mediated metabolic benefits of low-dose ultraviolet radiation in the mouse: a focus on brown adipose tissue

Non-burning (low-dose) UVR suppresses the BAT 'whitening', steatotic and pro-diabetic effects of consuming a high-fat diet through skin release of nitric oxide

The challenges of developing and optimising an assay to measure 25-hydroxyvitamin D in saliva

We have developed an LC-MS/MS assay that accurately measures saliva 25(OH)D3 levels, which correlated with serum levels

Inflammatory bowel diseases: interrelationships between dietary vitamin D, exposure to UV radiation and the fecal microbiome

This review explores the interaction of vitamin D, and ultraviolet radiation, with the intestinal innate and adaptive immune systems

Sun-immune connection

Exposure to ultraviolet radiation damages skin cell DNA but skin cancers develop because ultraviolet radiation also affects the immune system

Vitamin D metabolites are lower with active Crohn’s disease and spontaneously recover with development of remission

We aimed to characterise vitamin D metabolism in a cohort of patients with active and inactive Crohn’s disease

Exposure to Solar UVR Suppresses Cell-Mediated Immunization Responses in Humans: The Australian Ultraviolet Radiation and Immunity Study

Higher UVR exposure at antigen sensitization was associated with a reduced delayed-type hypersensitivity response and altered T helper type 17 kinetics

Exposure to Ultraviolet Radiation in the Modulation of Human Diseases

This review focuses primarily on the beneficial effects for human health of exposure to ultraviolet radiation

Tryptophan and arginine catabolic enzymes and regulatory cytokines in clinically isolated syndrome and multiple sclerosis

Higher IDO and ARG expression in clinically isolated syndrome and multiple sclerosis provides one sustained homeostatic mechanism to control multiple sclerosis-associated inflammation

Ultraviolet irradiation of skin alters the faecal microbiome independently of vitamin D in mice

Skin exposure to ultraviolet radiation alters the faecal microbiome, and further investigations to explore the implications of this in health and disease are warranted

High Dose Vitamin D supplementation alters faecal microbiome and predisposes mice to more severe colitis

High dose vitamin D supplementation is associated with a shift to a more inflammatory faecal microbiome and increased susceptibility to colitis

Higher Serum Immunoglobulin G3 Levels May Predict the Development of Multiple Sclerosis in Individuals With Clinically Isolated Syndrome

IgG3 levels and proportions of IgG3 (%IgG) in serum at CIS diagnosis were inversely correlated with the time until conversion to MS

Cellular and molecular mechanisms of vitamin D in food allergy

Epidemiological evidence from the past decade suggests a role of vitamin D in food allergy pathogenesis

A randomised, controlled clinical trial of narrowband UVB phototherapy for clinically isolated syndrome: The PhoCIS study

This study provides a basis for further studies to determine if there are any benefits of the therapeutic effects of narrowband UVB radiation on MS progression

Investigating the roles of regulatory T cells, mast cells and interleukin-9 in the control of skin inflammat roles of regulatory T cells, mast cells and interleukin-9 in the control of skin inflammation by vitamin D. Arch Dermatol Res. 2018;310(3):221-30.

We investigated the ability of topical 1,25(OH)2D to suppress contact dermatitis through an IL9 dependent process, examining mast cells and IL9 secreting cells.

Reticulon-1 and reduced migration toward chemoattractants by macrophages differentiated from the bone marrow of ultraviolet-irradiated and ultraviolet-chimeric mice

By using an anti-reticulon-1 Ab, a role for reticulon-1 in macrophage migration toward both CSF-1 and CCL2 was confirmed.

UV Irradiation of Skin Enhances Glycolytic Flux and Reduces Migration Capabilities in Bone Marrow–Differentiated Dendritic Cells

A systemic immunosuppression follows UV irradiation of the skin of humans and mice.

PGE2 pulsing of murine bone marrow cells reduces migration of daughter monocytes/macrophages in vitro and in vivo

Our results reveal long-lasting changes to progenitor cells of monocytes/macrophages by a 2-hour dimethyl PGE2 pulse that, in turn, limits the migration of their daughter cells to chemoattractants and inflammatory mediators.

Vitamin D supplementation of initially vitamin D-deficient mice diminishes lung inflammation with limited effects on pulmonary epithelial integrity

In disease settings, vitamin D may be important for maintaining optimal lung epithelial integrity and suppressing inflammation, but less is known of its effects prior to disease onset.

The bioenergetics of inflammation: insights into obesity and type 2 diabetes

Diabetes mellitus is one of the most common chronic metabolic disorders worldwide, and its incidence in Asian countries is alarmingly high.

Evolving Identification of Blood Cells Associated with Clinically Isolated Syndrome: Importance of Time since Clinical Presentation and Diagnostic MRI

This study aimed to identify a CIS peripheral blood signature that may provide clues for potential immunomodulatory approaches early in disease

Altered regulatory T-cell fractions and Helios expression in clinically isolated syndrome: clues to the development of multiple sclerosis

These results indicate that T regulatory (Treg) and follicular T regulatory (Tfr) impairment is an early feature in MS.

Sub-erythemal ultraviolet radiation reduces metabolic dysfunction in already overweight mice

Exposure to sunlight may limit cardiometabolic risk.

Are low sun exposure and/or Vitamin D risk factors for type 1 diabetes

Evidence supports that higher sun exposure and/or vitamin D sufficiency in pregnancy, or supplementation in early life, decreases type 1 diabetes risk

Introduction to the themed issue The health benefits of UV radiation exposure through Vitamin D production or non-Vitamin D pathways

The health benefits of UV radiation exposure through Vitamin D production or non-Vitamin D pathways

Vitamin D over the first decade and susceptibility to childhood allergy and asthma

We aimed to research relationships between 25(OH)D levels from birth to 10 y/o and susceptibility to allergic sensitization, respiratory issues and asthma.

Narrowband UVB phototherapy for clinically isolated syndrome: A trial to deliver the benefits of vitamin D and other UVB-induced molecules

The PhoCIS trial provides a fresh approach to re-defining the reported associations of 25(OH)D levels with multiple sclerosis development and progression

Molecular actions of Vitamin D in reproductive cell biology

The aim of this work is to review current metabolic and molecular aspects of the VitD-VitD receptor axis in reproductive medicine

High Vitamin D-Binding Protein Concentration, Low Albumin, and Mode of Remission Predict Relapse in Crohn's Disease

Associations between Vitamin D-binding protein, serum Vitamin D, and the calculated free Vitamin D concentrations with the risk of Crohn's disease flare

Vitamin D and allergic airway disease shape the murine lung microbiome in a sex-specific manner

Maintaining sufficient vitamin D is necessary for optimal lung health, and vitamin D may modulate the lung microbiome in a sex-specific fashion

Dietary Vitamin D Increases Percentages and Function of Regulatory T Cells in the Skin-Draining Lymph Nodes and Suppresses Dermal Inflammation

Dietary vitamin D3 increased the suppressive activity of regulatory T cells in the skin-draining lymph nodes, which are poised to suppress dermal inflammation

Identification of genes differentially regulated by vitamin D deficiency that alter lung pathophysiology and inflammation in allergic airways disease

Vitamin D deficiency exacerbates house dust mite-induced inflammation and alterations in lung structure and function

Serum 25-hydroxyvitamin D concentrations and cardiometabolic risk factors in adolescents and young adults

Associations between serum 25(OH)D concentrations and cardiometabolic risk factors from adolescence to young adulthood in the Raine Study

Heat-mediated reduction of apoptosis in UVB-damaged keratinocytes in vitro and in human skin ex vivo

UVB-induced p53-mediated cell cycle arrest and apoptosis are reduced in the presence of heat stress, leading to increased survival of DNA damaged cells

Cross-presentation of cutaneous melanoma antigen by migratory XCR1+CD103− and XCR1+CD103+ dendritic cells

This report provides new insight into the functional specialization within the broad network of dendritic cells that are responsible for skin immunosurveillance

UV Irradiation of Skin Regulates a Murine Model of Multiple Sclerosis.

The prevalence of multiple sclerosis follows a latitude gradient, with increased disease at higher latitudes.

Can skin exposure to sunlight prevent liver inflammation?

Here we discuss how skin exposure to sunlight may suppress liver inflammation and the severity of NAFLD.

Ultraviolet radiation, vitamin D and multiple sclerosis

Recent work highlights both vitamin D and non-vitamin D effects on cellular immunity that suggests that higher levels of sun exposure and/or vitamin D status...

The effects of in utero vitamin D deficiency on airway smooth muscle mass and lung function

In this study, we aimed to uncover the molecular mechanisms contributing to altered lung structure and function.

Comparing the effects of sun exposure and vitamin D supplementation on vitamin D insufficiency, and immune and cardio-metabolic function

Adults living in the sunny Australian climate are at high risk of skin cancer, but vitamin D deficiency (defined here as a serum 25-hydroxyvitamin D...

Vitamin D in fetal development: Findings from a birth cohort study

Birth cohort studies provide an invaluable resource for studies of the influence of the fetal environment on health in later life.

Reduced immune responses in chimeric mice engrafted with bone marrow cells from mice with airways inflammation.

During respiratory inflammation, it is generally assumed that dendritic cells differentiating from the bone marrow are immunogenic rather than immunoregulatory.

Vitamin D and immunity

The active form of vitamin D has an important role in calcium metabolism and in bone mineralisation, but the evidence for other health outcomes is mixed,...

Ultraviolet radiation suppresses obesity and symptoms of metabolic syndrome independently of vitamin D

UVR or sunlight exposure may be an effective means of suppressing the development of obesity and MetS, through mechanisms that are independent of vitamin D

Genome-wide association study of vitamin D levels in children: replication in the Western Australian Pregnancy Cohort (Raine) study

This genome-wide association study (GWAS) utilises data from the Western Australian Pregnancy Cohort (Raine) Study for 25-hydroxyvitamin D (25(OH)D) levels...

Vitamin D status and predictors of serum 25-hydroxyvitamin D concentrations in Western Australian adolescents

Using prospective data from the Western Australian Pregnancy Cohort (Raine) Study, we investigated vitamin D status and predictors of serum 25-hydroxyvitamin...

Low serum 25-hydroxyvitamin D concentrations associate with non-alcoholic fatty liver disease in adolescents independent of adiposity

This paper examined the link between low serum Vitamin D levels and development of non-alcoholic fatty liver disease (NAFLD) in adolescents between 14 and 17...

Vitamin D deficiency at 16 to 20 weeks' gestation is associated with impaired lung function and asthma at 6 years of age

This paper examines whether a Vitamin D deficiency during pregnancy affects the child's lung function predisposition towards lung disease such as asthma.

Maternal vitamin D status during pregnancy and bone mass in offspring at 20 years of age: A prospective cohort study

This longitudinal, prospective study investigated the association between maternal vitamin D status and peak bone mass of offspring in 341 mother and...

Vitamin D deficiency causes airway hyperresponsiveness and increases airway smooth muscle mass in the lungs of female BALB/c mice

We tested whether there is a causal association between vitamin D deficiency, airway smooth muscle (ASM) mass, and the development of airway hyperresponsiveness

Low maternal serum vitamin D during pregnancy and the risk for postpartum depression symptoms

Pregnancy is a time of vulnerability for vitamin D insufficiency, and there is an emerging literature associating low levels of 25(OH)-vitamin D with...

Immune cell trafficking from the brain maintains CNS immune tolerance

Evaluation of fluorescently labeled leukocyte migration in mice revealed that DCs travel via the RMS from the CNS to the cervical LNs (CxLNs), where they...

Dendritic cells and multiple sclerosis: Disease, tolerance and therapy

Multiple sclerosis (MS) is a devastating neurological disease that predominantly affects young adults resulting in severe personal and economic impact.

Low vitamin D levels are associated with symptoms of depression in young adult males

Results from studies examining associations between serum 25-hydroxyvitamin D (25(OH)D) concentrations and depressive symptoms are equivocal.

Characterization of regulatory dendritic cells differentiated from the bone marrow of UV-irradiated mice

In summary, UV-BMDCs do not express the classical phenotypic or gene expression properties of DCs reported by others as 'regulatory' or 'tolerogenic'.

Reversible Control by Vitamin D of Granulocytes and Bacteria in the Lungs of Mice: An Ovalbumin-Induced Model of Allergic Airway Disease

Vitamin D may be essential for restricting the development and severity of allergic diseases and asthma, but a direct causal link between vitamin D...

Maternal vitamin D levels during pregnancy and offspring eating disorder risk in adolescence

This is the first study to link low gestational vitamin D to increased eating disorder risk in female offspring of Caucasian mothers.

Altered immunity and dendritic cell activity in the periphery of mice after long-term engraftment with bone marrow from ultraviolet-irradiated mice

To investigate the immune capabilities of peripheral tissue DCs generated in vivo from the BM of UV-irradiated mice, chimeric mice were established.

Exposure to UV Wavelengths in Sunlight Suppresses Immunity. To What Extent is UV-induced Vitamin D3 the Mediator Responsible?

In experimental models, both vitamin D3-dependent and vitamin D3-independent pathways have been implicated in the mechanisms of UVR-induced systemic...

Prostaglandin E2 imprints a long-lasting effect on dendritic cell progenitors in the bone marrow

Injection of BM-differentiated DCs from nonchimeric mice restored the reduced immune responses of PGE2-chimeric mice.

Maternal Vitamin D Levels and the Autism Phenotype Among Offspring

We tested whether maternal vitamin D insufficiency during pregnancy is related to the autism phenotype.

Optimized 25-hydroxyvitamin D analysis using liquid-liquid extraction with 2D separation with LC/MS/MS detection, provides superior precision

The analysis of 25-hydroxyvitamin D3 (25(OH)D3) and related metabolites represents a considerable challenge for both clinical and research laboratories...

Immune modulation by UV: Role of vitamin D

In this chapter, evidence for and evidence against the involvement of vitamin D in the immunoregulatory properties of UV radiation is presented.

UVR-induced immunosupression

Despite considerable advances, the exact mechanism whereby UVR can lead to changes in immune responses is not entirely clear at present, and no...

The current state of play of rodent models to study the role of vitamin D in UV-induced immunomodulation

Ultraviolet radiation (UVR) from sunlight is immunomodulatory and the main source of vitamin D for humans.

Acute Erythemal Ultraviolet Radiation Causes Systemic Immunosuppression in the Absence

Vitamin D is synthesised by ultraviolet (UV) irradiation of skin and is hypothesized to be a direct mediator.

Toward homeostasis: Regulatory dendritic cells from the bone marrow of mice with inflammation

Inflammatory mediators from peripheral tissues may control dendritic cell (DC) development in the bone marrow.

Vitamin D supplementation, moderate sun exposure, and control of immune diseases

There is considerable debate about the benefits of vitamin D supplementation for multiple sclerosis, allergic asthma, and type 1 diabetes.

The anti-inflammatory actions of IL-4 in human monocytes are not mediated by IL-10, RP105 or the kinase activity of RIPK2

The anti-inflammatory actions of IL-4 in activated human monocytes may reflect transcriptional regulation of genes involved in TLR signaling pathways.

Maternal serum vitamin D levels during pregnancy and offspring neurocognitive development

The objective was to determine the association between maternal serum 25(OH)-vitamin D concentrations and behavioural, emotional and language outcomes...

Maternal Serum Vitamin D Levels During Pregnancy and Offspring Neurocognitive Development

New research links poor language to lack of Vitamin D in womb.

Vitamin D 3 deficiency enhances allergen-induced lymphocyte responses in a mouse model of allergic airway disease

In this study, using a mouse model, we determined whether vitamin D deficiency in utero and during early life modulated the severity of asthma.

Differences in control by UV radiation of inflammatory airways disease in naïve and allergen pre-sensitised mice

Exposure of skin to UV radiation (UVR) prior to allergen exposure can inhibit inflammatory airways disease in mice by reducing effector CD4+ T cells in both...

Modulation of the immune system by UV radiation: More than just the effects of vitamin D?

Humans obtain most of their vitamin D through the exposure of skin to sunlight

Vitamin D and atopy and asthma phenotypes in children: a longitudinal cohort study

Vitamin D has been linked in some studies with atopy- and asthma-associated phenotypes in children with established disease,but its role in disease inception...

Vitamin D deficiency causes deficits in lung function and alters lung structure

The prevalence of vitamin D deficiency is increasing and has been linked to obstructive lung diseases including asthma and chronic obstructive pulmonary disease

Immune mechanisms by which topically applied vitamin D acts as a therapeutic agent

Vitamin D, nutrition, diet, therapeutic agent

Ultraviolet irradiation of mice reduces the competency of bone marrow-derived CD11c+

Direct UV irradiation of dendritic cells and Langerhans cells reduces their Ag presenting ability. However, the effects of UV on CD11c(+) cells located...

Topical 1,25-dihydroxyvitamin D3 subverts the priming ability of draining lymph node dendritic cells

The active form of vitamin D, 1,25-hydroxyvitamin D(3) [1,25(OH)(2)D(3)] is produced in skin following exposure to sunlight

Gene regulation by 1,25-dihydroxyvitamin D3 in CD4+CD25+ cells is enabled by IL-2

Vitamin D may be responsible for reducing the development and severity of autoimmune and allergic diseases. Topically applied 1,25-dihydroxyvitamin D(3) (1,25(O

Immune-modifying properties of topical vitamin D: Focus on dendritic cells and T cells

Topical creams containing the active form of vitamin D (1,25-dihydroxyvitamin D3; 1,25(OH)2D3) or analogues of this compound are currently used with some succes

1,25-dihydroxyvitamin D3 enhances the ability of transferred CD4+ CD25+ cells to modulate T helper type 2-driven asthmatic responses

The severity of allergic diseases may be modified by vitamin D. However, the immune pathways modulated by the active form of vitamin D, 1,25-dihydroxyvitamin D.

Lentivirus-mediated gene transfer of interleukin 10 to the ovine and human cornea

Gene transfer to a donor cornea ex vivo can modulate corneal graft failure in experimental animal models. We compared a lentiviral vector (LV) carrying...

UV inhibits allergic airways disease in mice by reducing effector CD4 T cells

UV exposure and protection against allergic airways disease

Asthma is a chronic inflammatory disease of the small and large conducting airway mucosa characterised by Th2 cell immunity.