Functional manipulation of dendritic cells by photoswitchable generation of intracellular reactive oxygen species

Taek Chin Cheong, Eon Pil Shin, Eun Kyung Kwon, Ji Hye Choi, Kang Kyun Wang, Prashant Sharma, Kyong Hoon Choi, Jin Muk Lim, Hong Gee Kim, Keunhee Oh, Ju Hong Jeon, Insuk So, In Gyu Kim, Myung Sik Choi, Young-geun Kim, Seung Yong Seong, Yong Rok Kim, Nam Hyuk Cho

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13 Citations (Scopus)

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 Ca2+, 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.

Original languageEnglish
Pages (from-to)757-765
Number of pages9
JournalACS Chemical Biology
Volume10
Issue number3
DOIs
Publication statusPublished - 2015 Mar 20

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ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine

Cite this

Cheong, T. C., Shin, E. P., Kwon, E. K., Choi, J. H., Wang, K. K., Sharma, P., Choi, K. H., Lim, J. M., Kim, H. G., Oh, K., Jeon, J. H., So, I., Kim, I. G., Choi, M. S., Kim, Y., Seong, S. Y., Kim, Y. R., & Cho, N. H. (2015). Functional manipulation of dendritic cells by photoswitchable generation of intracellular reactive oxygen species. ACS Chemical Biology, 10(3), 757-765. https://doi.org/10.1021/cb5009124