A critical role for the proapoptotic protein bid in ultraviolet-induced immune suppression and cutaneous apoptosis.
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.
Pradhan
Sanjay
S
Department of Dermatology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Kim
Hee Kyung
HK
Thrash
Christopher J
CJ
Cox
Maureen A
MA
Mantena
Sudheer K
SK
Wu
Jian-He
JH
Athar
Mohammad
M
Katiyar
Santosh K
SK
Elmets
Craig A
CA
Timares
Laura
L
D000818:Animals; D017209:Apoptosis / Q000528:radiation effects*; D051017:Apoptosis Regulatory Proteins; D051023:BH3 Interacting Domain Death Agonist Protein / Q000502:physiology*; D007108:Immune Tolerance / Q000528:radiation effects; D007165:Immunosuppression Therapy; D015603:Keratinocytes / Q000166:cytology; D007801:Langerhans Cells / Q000166:cytology; D051379:Mice; D018345:Mice, Knockout; D012867:Skin / Q000166:cytology* / Q000528:radiation effects; D014466:Ultraviolet Rays
D051017:Apoptosis Regulatory Proteins; D051023:BH3 Interacting Domain Death Agonist Protein; C494815:Bid protein, mouse