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Notes: Background Ultraviolet (UV) B-induced effects on the skin immune system have been extensively investigated, but little is known regarding the immunological changes induced by UVA exposure of human skin. Recent data assessing the protection afforded by sunscreens against photoimmunosuppression stress the need for broad-spectrum sunscreens with an adequate UVA protection. Objectives The purpose of this study was first to determine the changes observed in epidermal Langerhans cells (ELC) density and epidermal antigen-presenting cell (APC) activity after exposure of human skin to UVAI (340–400 nm) radiation, and secondly to assess the immune protection afforded in vivo by a sunscreen formulation containing a long wavelength UVA filter with a low UVA protection factor (UVA-PF = 3). Methods Epidermal cell (EC) suspensions were prepared from skin biopsies 3 days after exposure to a single dose of UVAI (either 30 or 60 J cm−2). Results Flow-cytometric analysis of EC suspensions revealed that exposure to 60 J cm−2 UVAI resulted in a decreased number of ELC without infiltration of CD36+ DR+ CD1a– antigen-presenting macrophages into the epidermis, and a significant reduction of HLA-DR expression on viable ELC. In vivo exposure to both 30 and 60 J cm−2 resulted in a decreased allogeneic CD4+ T-cell proliferation induced by UVAI-irradiated ECs. The sunscreen application partially prevented (57 ± 9%) the decrease in epidermal allogeneic APC activity induced by 60 J cm−2 UVAI. Conclusions In vivo UVAI exposure of human skin results in a decreased number of ELC and in a downregulation of epidermal APC activity. This last effect is partially prevented by prior application of a sunscreen with a low UVAI-PF value. These results indicate that increasing the absorption of UV filters for long UVA wavelengths may lead to an improved immune protection.

Notes: Abstract: Sunscreens have been designed to protect against sunburn and their efficacy has, therefore, been labeled by the so-called sun protection factor (SPF). Although this value is well determined using a standardized protocol and it affords a good evaluation of the protection against erythema it may be inadequate to provide a relevant measurement of efficacy against other biologic damages. This is particularly true when action spectra and threshold dose are different from those of erythema. In the case of ultraviolet (UV)-induced immune suppression, the action spectrum is not known, so it cannot be asserted that SPF may accurately predict the level of protection against this endpoint. We addressed this issue by measuring in human volunteers the ability of two broad-spectrum SPF 15 sunscreens with different ultraviolet A (UVA) protection levels, to prevent the alteration of the efferent phase of the local delayed-type hypersensitivity (DTH) response to recall antigens (Multitest Pasteur/Mérieux, Lyon, France) after acute solar-simulated UV exposure. We first determined the ultraviolet radiation (UVR) dose needed to induce a significant DTH inhibition in several groups of 15 volunteers. Two minimal erythemal doses (2 MED) were found to be the minimal immunosuppressive dose (MISD). As a result, the immune DTH response is reduced in average by 36%. The lower doses tested (0.5 and 1 MED) were ineffective. Sunscreen-treated groups were exposed to either 1 or 2 MED × SPF doses. As expected, no alteration in DTH response was observed in the groups exposed to 1 MED × SPF whatever the sunscreen applied. In contrast, after exposure to 2 MED × SPF, the DTH response remained unaltered in the group pretreated with the sunscreen product with the higher protection in the UVA range but was significantly suppressed by 55.7% in the group pretreated with sunscreen with a much lower protection in the UVA range. These data suggest that SPF may not be sufficient to predict the ability of sunscreens to protect from UV-induced immune suppression. Determining the level of UVA protection is particularly needed, as UVA seems to have a relatively low contribution to erythema but is highly involved in immunosuppression.

Notes: Summary Background Ultraviolet (UV) exposure of human skin induces local and systemic immune suppression. This phenomenon has been well documented when UVB radiation (290–320 nm) is used. The mechanism is thought to involve Langerhans cells (LCs), the epidermal dendritic cells that play a crucial role in antigen presentation. A variety of studies have clearly demonstrated that UVB radiation decreases LC density and alters their morphology and immunological function, but little is known about the effects of the entire UV spectrum (ultraviolet solar simulated radiation, UV-SSR or UVB + UVA) or UVA (320–400 nm) radiation alone. Objectives The purpose of this study was to analyse and compare the effects of a single exposure of human volunteers to UV-SSR, total UVA or UVA1 (340–400 nm) in the human epidermal LC density and morphology. Methods Immunohistochemistry on epidermal sheets with various antibodies and transmission electron microscopy (TEM) were used. Results Immunostaining for class II antigen revealed that a single UV-SSR exposure, corresponding to twice the minimal erythemal dose (MED), induced a significant reduction in LC density with only slight morphological alterations of remaining cells. After a single UVA exposure, LC density showed a dose-dependent reduction with a significant effect at 60 J cm−2 (well above the MED). Moreover, the reduction of LC dendricity was also dose-dependent and significant for doses exceeding 30 J cm−2. UVA1 radiation was as effective as total UVA for the later endpoint. As demonstrated by TEM, the location of Birbeck granules containing epidermal cells was modified in UVA-exposed areas. They were located in the spinous rather than in the suprabasal layer. In addition, the morphology of these cells was altered. We observed a rounding up of the cell body with a reduction of dendricity. Alterations of mitochondrial membrane and ridges were also seen. Conclusions A single exposure of human skin in vivo to UV-SSR, UVA or UVA1 radiation results in different alterations of density and/or morphology of LCs. All these alterations may impair the antigen-presenting function of LCs leading to an alteration of immune response.