Nitric oxide induces human CLA + CD25 + Foxp3 + regulatory T cells with skin-homing potential

Yu, Cunjing; Fitzpatrick, Amanda; Cong, Duanduan; Yao, Chengcan; Yoo, Jinah; Turnbull, A.P.; Schwarze, Jürgen; Norval, Mary; Howie, Sarah; Weller, Richard; Astier, Anne

doi:10.1016/j.jaci.2017.05.023

Cited by 20 publications

(14 citation statements)

References 10 publications

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“… 11 , 27 UVR-induced nitric oxide has also been implicated in increased Treg induction in vivo. 28 Further studies will be required to determine if the circulating cells characterised in the blood of patients with MS 29 were altered by the phototherapy intervention.…”

Section: Discussionmentioning

confidence: 99%

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

Hart

Jones

Trend

et al. 2018

Multiple Sclerosis Journal - Experimental, Translational and Cl

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BackgroundThe natural history of multiple sclerosis (MS) typically presents with the clinically isolated syndrome (CIS), an episode of neurological symptoms caused by central nervous system inflammation or demyelination that does not fulfil the diagnostic criteria for MS.ObjectiveAs preclinical studies have suggested that exposure to ultraviolet radiation (UVR) could regulate the development of MS, the Phototherapy for CIS (PhoCIS trial) was established to examine the effects of narrowband UVB phototherapy on patients with CIS, and their conversion to MS.MethodsOf the 20 participants, half received 24 sessions of narrowband UVB exposure over eight weeks; participants in both arms were followed for 12 months. All participants were supplemented to 25-hydroxyvitamin D3 levels of >80 nmol/l.ResultsBy 12 months, 100% of those in the no phototherapy arm and 70% in the phototherapy arm had converted to MS, although this difference was not statistically significant.ConclusionThis 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.

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Section: Discussionmentioning

confidence: 99%

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

Hart

Jones

Trend

et al. 2018

Multiple Sclerosis Journal - Experimental, Translational and Cl

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“…Two skin-homing receptors were also measured on Treg cells in the context of UVR, chemokine receptor CCR4, and CLA (23, 56). CLA is a carbohydrate epitope induced by the α-(1,3)-fucosyltransferase VII gene and by cytokines and Ag stimulation (57-59), which is consistent with higher CD45RA − /CD27 − Treg cells.…”

Section: Discussionmentioning

confidence: 99%

T Regulatory Cell Subpopulations Associated with Recent Ultraviolet Radiation Exposure in a Skin Cancer Screening Cohort

Hesterberg

Amorrortu

Zhao

et al. 2018

The Journal of Immunology

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UV radiation (UVR) causing DNA damage is a well-documented risk factor for nonmelanoma skin cancer. Although poorly understood, UVR may also indirectly contribute to carcinogenesis by promoting immune evasion. To our knowledge, we report the first epidemiological study designed to investigate the association between quantitative measures of UVR, obtained using a spectrophotometer, and circulating T regulatory (Treg) cells. In addition to total Treg cells, the proportion of functionally distinct Treg cell subsets defined by CD45RA and CD27 phenotypic markers, graded expression of FOXP3 and CD25, and those expressing cutaneous lymphocyte–associated Ag and the chemokine receptor CCR4 were enumerated in 350 individuals undergoing routine skin cancer screening exams and determined not to have prevalent skin cancer. No associations were identified for UVR exposure or the overall proportion of circulating Treg cells; however, Treg cell subpopulations with an activation-associated phenotype, CD45RA−/CD27−, and those expressing cutaneous homing receptors were significantly positively associated with UVR. These subpopulations of Treg cells also differed by age, sex, and race. After stratification by natural skin tone, and adjusting for age and sex, we found that spectrophotometer-based measures of UVR exposure, but not self-reported measures of past sun exposure, were positively correlated with the highest levels of these Treg cell subpopulations, particularly among lighter-skinned individuals. Findings from this large epidemiologic study highlight the diversity of human Treg cell subpopulations associated with UVR, thus raising questions about the specific coordinated expression of CD45RA, CD27, CCR4, and cutaneous lymphocyte–associated Ag on Treg cells and the possibility that UVR contributes to nonmelanoma skin cancer carcinogenesis through Treg cell–mediated immune evasion.

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“…16 The metabolically beneficial effects of UVB have instead been linked to the release of nitric oxide from skin 10 with important anti-inflammatory effects also hypothesised for this pathway. 17 Recently published narrative reviews have described the potential for UVR (delivered as a phototherapy or through sun exposure advice) to modulate metabolic dysfunction in other pre-clinical and human clinical and epidemiological settings, [12][13][14] focusing on mediators through which UVR could act (i.e. through vitamin D-dependent and/or -independent pathways).…”

Section: Introductionmentioning

confidence: 99%

Systematic Review of the Effects of Ultraviolet Radiation on Markers of Metabolic Dysfunction

Gorman

Courten

Lucas

2019

CBR

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Emerging findings suggest that exposure to ultraviolet wavelengths of sunlight modulates metabolic function. Here we review the metabolic effects of exposure to ultraviolet radiation (UVR), focusing on the effects of phototherapies (that administer UVR), and advice to increase sun exposure in individuals enrolled in clinical trials and intervention studies. We identified 25 studies in which the effects of UVR on metabolic outcomes were examined, including: narrowband ultraviolet B phototherapy (nbUVB, n = 12); psoralen ultraviolet A phototherapy (n = 4); other types of UVR phototherapy (n = 5); and sun exposure advice (n = 5). Most studies recruited a small number of participants (≤100), who were middle-aged individuals undergoing treatment for psoriasis flare, with phototherapy or sun exposure advice administered for ≤12 weeks. Data obtained at baseline were usually compared with an endpoint following treatment with UVR, for a limited number of outcomes. There were few studies in which markers of glucose metabolism were assessed, with some beneficial effects of sun exposure (but not phototherapy) reported. LDL-cholesterol levels were lower in individuals receiving sun exposure advice, while treatment with nbUVB reduced blood concentrations of inflammatory markers (C-reactive protein and interleukin-6). Future studies should focus on determining whether the effects of these interventions change with time, and if they are dependent on the source of UVR (i.e. phototherapy or sun exposure) and wavelength(s) of light administered. Furthermore, studies need to measure a variety of (clinical) markers of glucose metabolism, adiposity and inflammation, control for factors such as skin type and sex, and stratify participants for metabolic disease diagnosis.

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Nitric oxide induces human CLA + CD25 + Foxp3 + regulatory T cells with skin-homing potential

Cited by 20 publications

References 10 publications

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

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

T Regulatory Cell Subpopulations Associated with Recent Ultraviolet Radiation Exposure in a Skin Cancer Screening Cohort

Systematic Review of the Effects of Ultraviolet Radiation on Markers of Metabolic Dysfunction

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