bcl-xL is critical for dendritic cell survival in vivo.
Dendritic cells (DC) are important regulators of immune function, transporting Ags from the periphery to draining lymph nodes (dLN) where they prime Ag-specific T lymphocytes. The magnitude of the immune response generated depends upon the longevity of the Ag-bearing DC in lymphoid tissues. We hypothesized that the control of DC survival is regulated by the antiapoptotic factor bcl-x(L). Gene gun immunization of dual-expression DNA vaccines into a bcl-x(fl/fl) mouse resulted in the delivery of Ag, as well as selective deletion of the bcl-x gene in directly transfected, skin-residing DC. bcl-x-deficient DC failed to mount effective immune responses, and this corresponded to their rapid disappearance from the dLN due to apoptosis. We confirmed these results using RNA interference to specifically silence the antiapoptotic bcl-x(L) isoform in targeted skin-residing DC of C57BL/6 mice. In addition, delivery of bcl-x(L) in trans complemented the bcl-x deficiency in DC of bcl-x(fl/fl) mice, resulting in the maintenance of normal levels of Ag-bearing DC in the dLN. Taken together, our work demonstrates that the bcl-x(L) isoform is critical for survival of skin-derived, Ag-bearing DC in vivo.
Hon
Huiming
H
Department of Microbiology and Immunology, Emory Vaccine Center, Emory University, Atlanta, GA 30329, USA.
Rucker
Edmund B
EB
Hennighausen
Lothar
L
Jacob
Joshy
J
D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis; D017209:Apoptosis / Q000235:genetics / Q000276:immunology; D019470:Biolistics / Q000379:methods; D039521:CD11c Antigen / Q000096:biosynthesis; D002465:Cell Movement / Q000235:genetics / Q000276:immunology; D002470:Cell Survival / Q000235:genetics / Q000276:immunology; D003713:Dendritic Cells / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D020868:Gene Silencing; D018390:Gene Targeting; D005816:Genetic Complementation Test; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000276:immunology; D008213:Lymphocyte Activation / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009976:Orthomyxoviridae Infections / Q000235:genetics / Q000276:immunology / Q000473:pathology; D020033:Protein Isoforms / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D034622:RNA Interference / Q000276:immunology; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology; D051020:bcl-X Protein
D000914:Antibodies, Viral; C494812:Bcl2l1 protein, mouse; D039521:CD11c Antigen; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D020033:Protein Isoforms; D019253:Proto-Oncogene Proteins c-bcl-2; D019444:Vaccines, DNA; D051020:bcl-X Protein