Review
The challenges of UV-induced immunomodulation for children’s health

https://doi.org/10.1016/j.pbiomolbio.2011.07.014Get rights and content

Abstract

Exposure to solar ultraviolet radiation (UVR) is recognised to have both beneficial and harmful effects on human health. With regard to immune responses, it can lead to suppression of immunity and to the synthesis of vitamin D, a hormone that can alter both innate and adaptive immunity. The consequences in children of such UV-induced changes are considerable: first there are positive outcomes including protection against some photoallergic (for example polymorphic light eruption) and T cell-mediated autoimmune diseases (for example multiple sclerosis) and asthma, and secondly there are negative outcomes including an increased risk of skin cancer (squamous cell carcinoma, basal cell carcinoma and cutaneous malignant melanoma) and less effective control of several infectious diseases. Many uncertainties remain regarding the amount of sun exposure that would provide children with the most effective responses against the variety of immunological challenges that they are likely to experience.

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)

  • H.E. Hanwell et al.

    Assessment of evidence for a protective role of vitamin D in multiple sclerosis

    Biochim. Biophys. Acta

    (2011)
  • M.L. Kripke

    Immunologic mechanisms in UV radiation carcinogenesis

    Adv. Cancer Res.

    (1981)
  • C.S. Lea et al.

    Ambient UVB and melanoma risk in the United States: a case–control analysis

    Ann. Epidemiol.

    (2007)
  • V. Madan et al.

    Non-melanoma skin cancer

    Lancet

    (2010)
  • D.D. Moyal et al.

    Broad-spectrum sunscreens provide better protection from the immunosuppression of the elicition phase of delayed-type hypersensitivity response in humans

    J. Invest. Dermatol.

    (2001)
  • S.V. Ramagopalan et al.

    Multiple sclerosis: risk factors, prodromes, and potential causal pathways

    Lancet Neurol.

    (2010)
  • A. Ray et al.

    A case for regulatory B cells in controlling the severity of autoimmune-mediated inflammation in experimental autoimmune encephalomyelitis and multiple sclerosis

    J. Neuroimmunol.

    (2011)
  • T. Schwarz et al.

    Molecular mechanisms of ultraviolet-radiation-induced immunosuppression. Eur

    J. Cell Biol.

    (2011)
  • A. Sleijffers et al.

    Ultraviolet radiation, reistance to infectious diseases, and vaccination responses

    Methods

    (2002)
  • F. Termorshuizen et al.

    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.

    (2002)
  • R.M. Van Dam et al.

    Diet and basal cell carcinoma of the skin in a prospective cohort of men

    Am. J. Clin. Nutr.

    (2000)
  • A.A. Vink et al.

    Cellular target of UVB-induced DNA damage resulting in local suppression of contact hypersensitivity

    J. Photochem. Photobiol. B. Biol.

    (1998)
  • S.E. Wenzel

    Asthma: defining of the persistent adult phenotypes

    Lancet

    (2006)
  • E.D. Acheson et al.

    The distribution of multiple sclerosis in U.S. veterans by birth place

    Am. J. Hyg.

    (1960)
  • H.K. Bayes et al.

    Timing of birth and risk of multiple sclerosis in the Scottish population

    Eur. Neurol.

    (2010)
  • B.R. Becklund et al.

    UV radiation suppresses experimental autoimmune encephalomyelitis independent of vitamin D production

    Proc. Natl. Acad. Sci. USA

    (2010)
  • S. Beissert et al.

    IL-12 prevents the inhibitory effects of cis-urocanic acid on tumor antigen presentation by Langerhans cells: implications for photocarcinogenesis

    J. Immunol.

    (2001)
  • D. Bikle

    Nonclassic actions of vitamin D

    J. Clin. Endocrinol. Metab.

    (2009)
  • D. Bruce et al.

    Vitamin D and host resistance to infection? Putting the cart in front of the horse

    Exp. Biol. Med.

    (2010)
  • S.N. Byrne et al.

    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.

    (2008)
  • C.A. Camargo et al.

    Cord-blood 25-hydroxyvitamin D levels and risk of respiratory infection, sneezing and asthma

    Pediatrics

    (2011)
  • R. Chacon-Salinas et al.

    Mast-cell-derived IL-10 suppresses germinal center formation by affecting T follicular helper cell function

    J. Immunol.

    (2011)
  • G.A. Colditz et al.

    Efficacy of BCG vaccine in the prevention of tuberculosis

    JAMA

    (1994)
  • F. Dalmay et al.

    Multiple sclerosis and solar exposure before the age of 15 years: case–control study in Cuba, Martinique and Sicily

    Mult. Scler.

    (2010)
  • N. Dehzaad et al.

    Regulatory T cells more effectively suppress Th1-induced airway inflammation compared with Th2

    J. Immunol.

    (2011)
  • K.M. Dixon et al.

    Vitamin D-defence

    Photochem. Photobiol. Sci.

    (2010)
  • A. Fukunaga et al.

    Langerhans cells serve as immunoregulatory cells by activating NKT cells

    J. Immunol.

    (2010)
  • C.R. Gale et al.

    Maternal vitamin D status during pregnancy and child outcomes

    Eur. J. Clin. Nutr.

    (2007)
  • N.K. Gibbs et al.

    Recent advances in urocanic acid photochemistry, photobiology and photoimmunology

    Photochem. Photobiol. Sci.

    (2008)
  • S. Gorman et al.

    Primary defect in UVB-induced systemic immunomodulation does not relate to immature or functionally impaired APCs in regional lymph nodes

    J. Immunol.

    (2005)
  • S. Gorman et al.

    UV exposure and protection against allergic airways disease

    Photochem. Photobiol. Sci.

    (2010)
  • M.A. Grimbaldeston et al.

    Mast cells in photodamaged skin: what is their role in skin cancer?

    Photochem. Photobiol. Sci.

    (2006)
  • A. Gruber-Wackernagel et al.

    Randomized double-blinded placebo-controlled intra-individual trial on 1, 25-(OH)2 vitamin D3 analogue in polymorphic light eruption

    Br. J. Dermatol.

    (2011)
  • E. Hamelmann et al.

    IL-5-induced airway eosinophilia – the key to asthma?

    Immuno. Rev.

    (2001)
  • S.R. Hammond et al.

    The epidemiology of multiple sclerosis in three Australian cities: Perth, Newcastle and Hobart

    Brain

    (1988)
  • S.R. Hammond et al.

    The age-range of risk of developing multiple sclerosis: evidence from a migrant population in Australia

    Brain

    (2000)
  • A.E. Handel et al.

    Environmental factors and their timing in adult-onset multiple sclerosis

    Nat. Rev. Neurol.

    (2010)
  • W.L. Ho et al.

    Update on the pathogenesis of post-transplant skin cancer in renal transplant recipients

    Br. J. Dermatol.

    (2008)
  • M.F. Holick

    Vitamin D; a millennium perspective

    J. Cell Biochem.

    (2003)
  • I. Horkay et al.

    Photosensitivity skin disorders in childhood

    Photodermatol. Photoimmunol. Photomed.

    (2008)
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