ReviewThe challenges of UV-induced immunomodulation for children’s health
Introduction
Exposure to sunlight has both beneficial and harmful outcomes. The sun provides warmth and a sense of well-being, as well as being essential for controlling biorhythms. It is also required for the synthesis of vitamin D in the skin. Solar ultraviolet radiation (UVR) can suppress immunity to antigens experienced within a short period after the exposure. This was first demonstrated about 35 years ago by Margaret Kripke and colleagues using highly antigenic tumour cells derived from chronically irradiated mice which were transferred to syngeneic naïve mice: if these recipients were UV-irradiated prior to the transfer, the cells were not rejected but grew into tumours (Kripke and Fisher, 1976). Other antigens including contact sensitisers, alloantigens and microorganisms have been tested since then in model systems, and the same down-regulation found. More limited approaches in human subjects indicate that a similar response is induced as in the models. Exposure to solar UVR is thought to induce much of the vitamin D in most individuals. Vitamin D has many effects on human health including the capacity to affect both innate and adaptive immune responses. The consequences of the immunosuppression and the vitamin D production that follow UVR are complex, some considered positive and some negative.
In this article, the effects of UVR on human immune responses are assessed, particularly those relating to children’s health. The first section below contains overviews of the pathways leading to UV-induced immunosuppression and to UV-induced vitamin D together with its immunological properties. This is followed by illustrations of the protective role of UVR against some photoallergic and autoimmune diseases and against asthma. Next illustrations of the detrimental aspects of UVR on immunity are described, namely the increased risk of skin cancer and the less effective control of infections. Lastly some conclusions are reached concerning the best advice to offer to the public regarding the sun exposure that would provide children with the optimal “immunological health”.
Section snippets
Effects of UVR on immune responses
These fall into two categories, first the cascade that leads to suppression of immunity and secondly the production of cutaneous vitamin D which can subsequently modulate immune responses. Brief descriptions of both aspects follow.
Beneficial effects of UV-induced immunosuppression on the health of children
There are several instances where the down-regulation in immunity as a result of UVR can confer positive health outcomes in children. First there is protection against photosensitive disorders: polymorphic light eruption (PLE) is used as an example (see Section 3.1 below). Secondly there is protection against the T cell-mediated autoimmune diseases: multiple sclerosis (MS) is used as an example (see Section 3.2 below). Thirdly asthma is considered (see Section 3.3 below).
Detrimental effects of UV-induced immunosuppression on the health of children
While the sections above describe some potential advantages of UV-induced immunomodulation on the health of children, there can also be significant adverse effects, as illustrated by the induction of skin cancer and by the reduced control of selected infectious diseases and efficacy of vaccination.
Conclusions
This review has assessed the evidence available currently regarding the effects of solar UVR on human health, especially relating to the health of children. UVR is recognised to suppress T cell immunity and to induce vitamin D which itself alters many immune parameters. There are robust results indicating several beneficial outcomes of UVR including protection against photoallergy and some autoimmune diseases, and several adverse outcomes including the increased risk of skin cancer. Other
References (108)
- et al.
The effect of ultraviolet radiation on humoral immune responses to T-dependent antigens
Environ. Res.
(1986) - et al.
The epidemiology of UV induced skin cancer
J. Photochem. Photobiol. B. Biol.
(2001) - et al.
Vitamin D and multiple sclerosis
Lancer Neurol.
(2010) - et al.
Association of prediagnostic serum vitamin D levels with the development of basal cell carcinoma
J. Invest. Dermatol.
(2010) - et al.
Estimation of optimal serum concentration of 25-hydroxyvitamin D for multiple health outcomes
Am. J. Clin. Nutr.
(2006) - et al.
B cells activated in lymph nodes in response to ultraviolet irradiation or by interleuin-10 inhibit dendritic cell induction of immunity
J. Invest. Dermatol.
(2005) - et al.
Maternal intake of vitamin D during pregnancy and risk of recurrent wheeze in children at 3 y of age
Am. J. Clin. Nutr.
(2007) - et al.
Ultraviolet radiation induced suppression of Mantoux reaction in humans
J. Invest. Dermatol.
(1998) - et al.
Maternal vitamin D intake during pregnancy and early childhood wheezing
Am. J. Clin. Nutr.
(2007) - et al.
Melanoma and vitamin D
Mol. Oncol.
(2011)
Assessment of evidence for a protective role of vitamin D in multiple sclerosis
Biochim. Biophys. Acta
Immunologic mechanisms in UV radiation carcinogenesis
Adv. Cancer Res.
Ambient UVB and melanoma risk in the United States: a case–control analysis
Ann. Epidemiol.
Non-melanoma skin cancer
Lancet
Broad-spectrum sunscreens provide better protection from the immunosuppression of the elicition phase of delayed-type hypersensitivity response in humans
J. Invest. Dermatol.
Multiple sclerosis: risk factors, prodromes, and potential causal pathways
Lancet Neurol.
A case for regulatory B cells in controlling the severity of autoimmune-mediated inflammation in experimental autoimmune encephalomyelitis and multiple sclerosis
J. Neuroimmunol.
Molecular mechanisms of ultraviolet-radiation-induced immunosuppression. Eur
J. Cell Biol.
Ultraviolet radiation, reistance to infectious diseases, and vaccination responses
Methods
A review of studies on the effects of ultraviolet irradiation on the resistance to infections: evidence from rodent infection models and verification by experimental and observational human studies
Int. Immunopharmacol.
Diet and basal cell carcinoma of the skin in a prospective cohort of men
Am. J. Clin. Nutr.
Cellular target of UVB-induced DNA damage resulting in local suppression of contact hypersensitivity
J. Photochem. Photobiol. B. Biol.
Asthma: defining of the persistent adult phenotypes
Lancet
The distribution of multiple sclerosis in U.S. veterans by birth place
Am. J. Hyg.
Timing of birth and risk of multiple sclerosis in the Scottish population
Eur. Neurol.
UV radiation suppresses experimental autoimmune encephalomyelitis independent of vitamin D production
Proc. Natl. Acad. Sci. USA
IL-12 prevents the inhibitory effects of cis-urocanic acid on tumor antigen presentation by Langerhans cells: implications for photocarcinogenesis
J. Immunol.
Nonclassic actions of vitamin D
J. Clin. Endocrinol. Metab.
Vitamin D and host resistance to infection? Putting the cart in front of the horse
Exp. Biol. Med.
Mast cell migration from the skin to the draining lymph nodes upon ultraviolet irradiation represents a key step in the induction of immune suppression
J. Immunol.
Cord-blood 25-hydroxyvitamin D levels and risk of respiratory infection, sneezing and asthma
Pediatrics
Mast-cell-derived IL-10 suppresses germinal center formation by affecting T follicular helper cell function
J. Immunol.
Efficacy of BCG vaccine in the prevention of tuberculosis
JAMA
Multiple sclerosis and solar exposure before the age of 15 years: case–control study in Cuba, Martinique and Sicily
Mult. Scler.
Regulatory T cells more effectively suppress Th1-induced airway inflammation compared with Th2
J. Immunol.
Vitamin D-defence
Photochem. Photobiol. Sci.
Langerhans cells serve as immunoregulatory cells by activating NKT cells
J. Immunol.
Maternal vitamin D status during pregnancy and child outcomes
Eur. J. Clin. Nutr.
Recent advances in urocanic acid photochemistry, photobiology and photoimmunology
Photochem. Photobiol. Sci.
Primary defect in UVB-induced systemic immunomodulation does not relate to immature or functionally impaired APCs in regional lymph nodes
J. Immunol.
UV exposure and protection against allergic airways disease
Photochem. Photobiol. Sci.
Mast cells in photodamaged skin: what is their role in skin cancer?
Photochem. Photobiol. Sci.
Randomized double-blinded placebo-controlled intra-individual trial on 1, 25-(OH)2 vitamin D3 analogue in polymorphic light eruption
Br. J. Dermatol.
IL-5-induced airway eosinophilia – the key to asthma?
Immuno. Rev.
The epidemiology of multiple sclerosis in three Australian cities: Perth, Newcastle and Hobart
Brain
The age-range of risk of developing multiple sclerosis: evidence from a migrant population in Australia
Brain
Environmental factors and their timing in adult-onset multiple sclerosis
Nat. Rev. Neurol.
Update on the pathogenesis of post-transplant skin cancer in renal transplant recipients
Br. J. Dermatol.
Vitamin D; a millennium perspective
J. Cell Biochem.
Photosensitivity skin disorders in childhood
Photodermatol. Photoimmunol. Photomed.
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