A Critical Role for the Proapoptotic Protein Bid in Ultraviolet-Induced Immune Suppression and Cutaneous Apoptosis

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.

Dendritic cells: ultrastructural and immunophenotypical changes upon nb-UVB in vitiligo skin

“…Specifically, it was not possible to detect the presence of the typical Birbeck granule in lesional skin. After nb-UVB exposure, in fact, there is a replacement of Langerhans cells, which have migrated to the dermis, by immature precursors [15]. This CD83 expression reduction, on the other hand, was not observed in the lesional dermis of vitiligo skin where there is an increase of 25%.…”

Dendritic Cell Apoptosis: Regulation of Tolerance versus Immunity

“…Immature DCs (both human and mouse) are highly susceptible to UVB radiation, whereas mature DCs upregulate c-FLIP and Bcl-2 and are less susceptible to UV-induced apoptosis (52). Prevention of apoptosis of Langerhans cells blocks UV-induced immunosuppression, suggesting that UVinduced DC apoptosis makes viable DCs tolerogenic; however, the mechanism remains unclear (53).…”

Mouse 3T3-L1 cells acquire resistance against oxidative stress as the adipocytes differentiate via the transcription factor FoxO

“…The former is activated under oxidative stress conditions, after exposure to ultraviolet rays, and under physical stress conditions such as heat shock [13][14][15][16], and the latter is activated by physiological ligands such as TNF-a, TNF-related apoptosis inducing ligand, and Fas ligand [17,18]. The activation of any of the two pathways results in the apoptosis of tumor cells and unwanted cells.…”