title: Functional manipulation of dendritic cells by photoswitchable generation of intracellular reactive oxygen species.
abstract: Reactive oxygen species (ROS) play an important role in cellular signaling as second messengers. However, studying the role of ROS in physiological redox signaling has been hampered by technical difficulties in controlling their generation within cells. Here, we utilize two inert components, a photosensitizer and light, to finely manipulate the generation of intracellular ROS and examine their specific role in activating dendritic cells (DCs). Photoswitchable generation of intracellular ROS rapidly induced cytosolic mobilization of Ca(2+), differential activation of mitogen-activated protein kinases, and nuclear translocation of NF-κB. Moreover, a transient intracellular ROS surge could activate immature DCs to mature and potently enhance migration in vitro and in vivo. Finally, we observed that intracellular ROS-stimulated DCs enhanced antigen specific T-cell responses in vitro and in vivo, which led to delayed tumor growth and prolonged survival of tumor-bearing mice when immunized with a specific tumor antigen. Therefore, a transient intracellular ROS surge alone, if properly manipulated, can cause immature DCs to differentiate into a motile state and mature forms that are sufficient to initiate adaptive T cell responses in vivo.
authors.forename: Taek-Chin
authors.initials: TC
authors.lastname: Cheong
authors.affiliation: ⊥Department of Chemistry, Yonsei University, Seoul, Republic of Korea.
authors.forename: Eon Pil
authors.initials: EP
authors.lastname: Shin
authors.forename: Eun-Kyung
authors.initials: EK
authors.lastname: Kwon
authors.forename: Ji-Hye
authors.initials: JH
authors.lastname: Choi
authors.affiliation: ⊥Department of Chemistry, Yonsei University, Seoul, Republic of Korea.
authors.forename: Kang-Kyun
authors.initials: KK
authors.lastname: Wang
authors.forename: Prashant
authors.initials: P
authors.lastname: Sharma
authors.affiliation: ⊥Department of Chemistry, Yonsei University, Seoul, Republic of Korea.
authors.forename: Kyong Hoon
authors.initials: KH
authors.lastname: Choi
authors.affiliation: #Biomedical Knowledge Engineering Laboratory, Dental Research Institute and Institute of Human-Environment Interface Biology, Seoul National University, Seoul, Republic of Korea.
authors.forename: Jin-Muk
authors.initials: JM
authors.lastname: Lim
authors.affiliation: #Biomedical Knowledge Engineering Laboratory, Dental Research Institute and Institute of Human-Environment Interface Biology, Seoul National University, Seoul, Republic of Korea.
authors.forename: Hong-Gee
authors.initials: HG
authors.lastname: Kim
authors.forename: Keunhee
authors.initials: K
authors.lastname: Oh
authors.forename: Ju-Hong
authors.initials: JH
authors.lastname: Jeon
authors.forename: Insuk
authors.initials: I
authors.lastname: So
authors.forename: In-Gyu
authors.initials: IG
authors.lastname: Kim
authors.forename: Myung-Sik
authors.initials: MS
authors.lastname: Choi
authors.affiliation: ▽Department of Materials Science and Engineering, Korea University, Seoul, Republic of Korea.
authors.forename: Young Keun
authors.initials: YK
authors.lastname: Kim
authors.forename: Seung-Yong
authors.initials: SY
authors.lastname: Seong
authors.affiliation: ⊥Department of Chemistry, Yonsei University, Seoul, Republic of Korea.
authors.forename: Yong-Rok
authors.initials: YR
authors.lastname: Kim
authors.forename: Nam-Hyuk
authors.initials: NH
authors.lastname: Cho
mesh_terms: D056704:Adaptive Immunity / Q000187:drug effects* / Q000528:radiation effects; D000818:Animals; D000951:Antigens, Neoplasm / Q000008:administration & dosage*; D002118:Calcium / Q000276:immunology / Q000378:metabolism; D020013:Calcium Signaling; D045744:Cell Line, Tumor; D002465:Cell Movement; D003110:Colonic Neoplasms / Q000235:genetics / Q000276:immunology / Q000401:mortality / Q000628:therapy*; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology / Q000473:pathology / Q000528:radiation effects; D015972:Gene Expression Regulation, Neoplastic / Q000276:immunology*; D006415:Hematoporphyrins / Q000494:pharmacology; D007114:Immunization; D008027:Light; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016328:NF-kappa B / Q000235:genetics / Q000276:immunology; D017319:Photosensitizing Agents / Q000494:pharmacology; D061251:Primary Cell Culture; D021381:Protein Transport; D017382:Reactive Oxygen Species / Q000819:agonists* / Q000276:immunology / Q000378:metabolism; D016019:Survival Analysis; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics / Q000276:immunology
chemical_list: D000951:Antigens, Neoplasm; D006415:Hematoporphyrins; D016328:NF-kappa B; D017319:Photosensitizing Agents; D017382:Reactive Oxygen Species; D048051:p38 Mitogen-Activated Protein Kinases; D002118:Calcium