Resolvin E1 inhibits dendritic cell migration in the skin and attenuates contact hypersensitivity responses

J Exp Med. 2015 Oct 19;212(11):1921-30. doi: 10.1084/jem.20150381. Epub 2015 Oct 5.

Abstract

Resolvin E1 (RvE1) is a lipid mediator derived from ω3 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / chemistry
  • Animals
  • Cell Movement / drug effects*
  • Cells, Cultured
  • Dendritic Cells / drug effects*
  • Dendritic Cells / physiology
  • Dermatitis, Contact / drug therapy*
  • Eicosapentaenoic Acid / analogs & derivatives*
  • Eicosapentaenoic Acid / pharmacology
  • Female
  • Interferon-gamma / biosynthesis
  • Leukotriene B4 / physiology
  • Mice
  • Mice, Inbred C57BL
  • Receptors, Leukotriene B4 / physiology
  • Skin / immunology*

Substances

  • Actins
  • Ltb4r1 protein, mouse
  • Receptors, Leukotriene B4
  • Leukotriene B4
  • Interferon-gamma
  • Eicosapentaenoic Acid
  • 5S,12R,18R-trihydroxy-6Z,8E,10E,14Z,16E-eicosapentaenoic acid