-
[show abstract]
[hide abstract]
ABSTRACT: Neonates have a developing immune response, with a predisposition towards induction of tolerance. As the immune system develops, immunity rather than tolerance is induced, with this development of immunity occurring in response to external factors such as the environment. As ultraviolet radiation (UVR) suppresses immunity, it is likely that the effect of UVR on the neonatal immune system would be augmentation of the suppressive response. In support, childhood exposure to UVR has been linked with an increased incidence of melanoma; consistent with an increase in suppression. To address this, phenotypic and functional immune system studies were undertaken at 8 weeks after one single exposure of solar-simulated UVR to mice, when mice had reached adulthood. Subtle changes were observed in cell populations resident in the skin-draining lymph nodes (LNs) and there also appeared to be a subtle, but not statistically significant, increase in the production of interleukin-10 and interferon-γ. Importantly, these changes also corresponded with significant suppression of the contact hypersensitivity response in irradiated mice compared with their control counterparts. This suppression was apparent when antigen sensitisation occurred during the neonatal or adult period, and thus did not appear to be analogous to UVR-induced suppression in adults. Although the percentage of T regulatory cells was increased in the skin-draining LNs, they were induced in a different manner to those induced following adult UVR exposure, with no increase in function on a per-cell basis. It therefore appears that one single neonatal exposure to UVR alters development of the immune system, leading to long-term implications for induction of immunity.
Immunology and Cell Biology 01/2011; 89(7):767-76. · 3.66 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Evaluation of: Hatton JL, Parent A, Tober KL et al. Depletion of CD4+ cells exacerbates the cutaneous response to acute and chronic UVB exposure. J. Invest. Dermatol. 127, 1507-1515 (2007).And: Loser K, Apelt J, Voskort M et al. IL-10 controls ultraviolet-induced carcinogenesis in mice. J. Immunol. 179, 365-371 (2007).Skin cancer represents the commonest form of human cancer in fair-skinned people, with the most important risk factors being life-time exposure to sunlight and episodes of severe sunburning. The two papers discussed here examine critical immunological parameters that protect against skin cancer development in mice chronically exposed to UV radiation. CD4+ T cells were shown to limit the cutaneous inflammatory response to acute UV exposure, and these cells protected against photocarcinogenesis by regulating inflammation in the skin. IL-10, presumably produced by CD4+CD25+ T regulatory cells, was revealed to be a crucial immunosuppressive agent in photocarcinogenesis. Based on these results, strategies to prevent or lessen the risk of skin cancer development are suggested.
Expert Review of Dermatology 09/2007; 2(5):543-547.
-
[show abstract]
[hide abstract]
ABSTRACT: The Skin Immune System (SIS) is a relatively new concept central to the issue of cutaneous tumour surveillance. The Langerhans cell (LC) is a key component of SIS. Skin cancer causing agents such as ultraviolet B (UV-B) irradiation and chemical carcinogens like dimethylbenz(a)anthracene (DMBA) alter LC function, resulting in immunosuppression and the promotional phase of tumour development. Once tumours, such as melanoma, are established they may show evidence of tumour regression due to immune reaction but frequently escape immune attack and metastasise. This article explores our knowledge of LC and SIS in these responses. For tumour immunosurveillance to be an effective reality at the clinical level, experiments are required to provide a more precise base for immunotherapy.
European journal of dermatology: EJD 15(2):63-9. · 2.53 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The neonatal immune environment and the events that occur during this time have profound effects for the adult period. While protective immune responses can develop, the neonatal immune system, particularly the skin immune system (SIS), tends to promote tolerance. With this information we undertook a number of studies to identify unique aspects of skin during the neonatal period. Proteomics revealed proteins uniquely expressed in neonatal, but not adult, skin (e.g. Stefin A, peroxiredoxins) and these may have implications in the development of SIS. Vitamin D was found to have a modulating role on SIS and this was apparent from the early neonatal period. Exposure of the neonatal skin to UV radiation altered the microenvironment resulting in the generation of regulatory T cells, which persisted in adult life. As the development of UV radiation-induced melanoma can occur following a single high dose (equivalent to burning in adults) to transgenic mice (hepatocyte growth factor/scatter factor or TPras) during the neonatal period, the early modulating events which lead to suppression may be relevant for the development of UV radiation-induced human melanoma. Any attempt to produce effective melanoma immunotherapy has to accommodate and overcome these barriers. Margaret Kripke's pioneering work on UV-induced immunosuppression still remains central to the understanding of the development of melanoma and how it frequently escapes the immune system.
Photochemistry and Photobiology 84(1):47-54. · 2.41 Impact Factor
