Journal
JOURNAL OF EXPERIMENTAL MEDICINE
Volume 212, Issue 11, Pages 1921-1930Publisher
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20150381
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Funding
- Ministry of Education, Culture, Sports, Science and Technology
- Ministry of Health, Labour and Welfare of Japan
- Precursory Research for Embryonic Science and Technology
- Japan Agency for Medical Research and Development
- Japanese Society for Investigative Dermatology's Fellowship SHISEIDO Award
- Grants-in-Aid for Scientific Research [15H04708, 22116001, 13J02446, 15H05790, 15H05904] Funding Source: KAKEN
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Resolvin E1 (RvE1) is a lipid mediator derived from omega 3 polyunsaturated fatty acids that exerts potent antiinflammatory roles in several murine models. The antiinflammatory mechanism of RvE1 in acquired immune responses has been attributed to attenuation of cytokine production by dendritic cells (DCs). In this study, we newly investigated the effect of RvE1 on DC motility using two-photon microscopy in a contact hypersensitivity (CHS) model and found that RvE1 impaired DC motility in the skin. In addition, RvE1 attenuated T cell priming in the draining lymph nodes and effector T cell activation in the skin, which led to the reduced skin inflammation in CHS. In contrast, leukotriene B4 (LTB4) induced actin filament reorganization in DCs and increased DC motility by activating Cdc42 and Rac1 via BLT1, which was abrogated by RvE1. Collectively, our results suggest that RvE1 attenuates cutaneous acquired immune responses by inhibiting cutaneous DC motility, possibly through LTB4-BLT1 signaling blockade.
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