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ABSTRACT: Apoptosis plays an important role in eliminating UV-damaged keratinocytes, but its role in UV-induced immune suppression is not clear. Langerhans cells (LCs) may function as inducers of immune suppression. We have shown that LCs derived from mice deficient in the proapoptotic Bid (BH3-interacting death domain protein) gene (Bid KO) resist apoptosis and induce amplified immune responses. In this report, we examined responses in Bid KO mice to UVB exposure. Acute UV exposure led Bid KO mice to develop fewer apoptotic cells and retain a greater fraction of LCs in the epidermal layer of skin in comparison to wild-type mice. Bid KO mice were also markedly resistant to local and systemic UV tolerance induction to hapten sensitization and contact hypersensitivity responses. Elicitation responses and inflammation at skin sensitization sites in UV-treated Bid KO mice were equal to or greater than nonsuppressed control responses. In Bid KO mice, LCs accumulated in lymph nodes to greater numbers, demonstrated longer lifespans, and contained fewer DNA-damaged cells. These studies provide evidence that Bid activation is a critical upstream mediator in UV-induced keratinocyte and LC apoptosis and that its absence abrogates UV-induced immune tolerance.
The Journal of Immunology 10/2008; 181(5):3077-88. · 5.79 Impact Factor
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ABSTRACT: The fate of dendritic cells (DCs) after Ag presentation may be DC subset-specific and controlled by many factors. The role of activation-induced apoptosis in regulating DC function is not clear. We investigated the fate of cutaneous DCs (cDCs), specifically Langerhans cells (LCs), and observed that they undergo apoptosis after successful Ag presentation to CD4 T cells. Caspase-specific inhibitors revealed that LC lines use a type II apoptosis pathway in response to CD4 T cells. In support of this, BH3-interacting domain (Bid) protein was present at high levels and specifically cleaved in the presence of Ag-specific T cells. Significant resistance to apoptosis by OT-2 CD4 cells was also observed for Bid knockout (KO) LCs in vitro. To test whether Bid was required to regulate LC function in vivo, we measured contact sensitization and topical immunization responses in Bid KO mice and observed markedly enhanced ear swelling and proliferation responses compared with wild-type mice. Furthermore, when Ag-pulsed Bid KO migratory cDCs were inoculated into wild-type recipients, an increase in both the rate and percentage of expanded OT-2 T cells expressing IFN-gamma was observed. Thus, enhanced Ag presentation function was intrinsic to Bid KO cDCs. Therefore, Bid is an important regulator of LC viability and Ag presentation function.
The Journal of Immunology 12/2006; 177(9):5956-67. · 5.79 Impact Factor
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ABSTRACT: Sunscreens applied to the skin are retained primarily in the stratum corneum, where they adsorb and act as a barrier preventing UV penetration to deeper layers. Photophysical properties of sunscreens have traditionally been studied either in solvents, which are very different from skin, or in skin or complex artificial skin systems, which are difficult to handle. The purpose of this study was to determine whether polystyrene nanospheres could serve as an improvement over solvents for evaluation of the photophysical properties of sunscreens without the presence of autofluorescence from and interactions with specific skin biomolecules. We used HaCat cells and excised skin for this comparative study with nanospheres. Fluorescence spectral properties of common hydrophobic sunscreens octyl salicylate, padimate O (2-ethylhexyl-4-dimethylaminobenzoate) and octyl methoxycinnamate adsorbed to 220 nm polystyrene spheres are similar to those of sunscreens adsorbed to HaCat cells and excised skin. Specifically, similarity in the emission peaks and their approximate positions, excitation peak positions and a measurable reduction in scattering upon sunscreen addition suggest that polystyrene nanospheres constitute a useful system to evaluate the photophysical properties of topical sunscreens and may serve as a model system for high-throughput evaluation of potential sunscreens. An unexpected result of this comparative study was the observation of an increase in a specific skin component emission caused by addition of padimate O.
Photochemistry and Photobiology 82(6):1557-65. · 2.41 Impact Factor
