DICAM in the Extracellular Vesicles from Astrocytes Attenuates Microglia Activation and Neuroinflammation

Jin Han; Hyun-Jung Cho; Donghwi Park; Seungwoo Han

doi:10.3390/cells11192977

DICAM in the Extracellular Vesicles from Astrocytes Attenuates Microglia Activation and Neuroinflammation

Cells. 2022 Sep 24;11(19):2977. doi: 10.3390/cells11192977.

Authors

Jin Han¹, Hyun-Jung Cho², Donghwi Park³, Seungwoo Han^{1

4}

Affiliations

¹ Laboratory for Arthritis and Cartilage Biology, Research Institute of Aging and Metabolism, Kyungpook National University, Daegu 41404, Korea.
² Laboratory for Arthritis and Bone Biology, Fatima Research Institute, Daegu Fatima Hospital, Daegu 41404, Korea.
³ Department of Physical Medicine and Rehabilitation, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan 44521, Korea.
⁴ Division of Rheumatology, Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu 41404, Korea.

Abstract

Cross-talk between astrocytes and microglia plays an important role in neuroinflammation and central sensitization, but the manner in which glial cells interact remains less well-understood. Herein, we investigated the role of dual immunoglobulin domain-containing cell adhesion molecules (DICAM) in the glial cell interaction during neuroinflammation. DICAM knockout (KO) mice revealed enhanced nociceptive behaviors and glial cell activation of the tibia fracture with a cast immobilization model of complex regional pain syndrome (CRPS). DICAM was selectively secreted in reactive astrocytes, mainly via extracellular vesicles (EVs), and contributed to the regulation of neuroinflammation through the M2 polarization of microglia, which is dependent on the suppression of p38 MAPK signaling. In conclusion, DICAM secreted from reactive astrocytes through EVs was involved in the suppression of microglia activation and subsequent attenuation of neuroinflammation during central sensitization.

Keywords: CRPS; DICAM; astrocyte; extracellular vesicle; microglia; neuroinflammation.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Astrocytes* / metabolism
Cell Adhesion Molecules / metabolism
Extracellular Vesicles* / metabolism
Mice
Mice, Knockout
Microglia / metabolism
Neuroinflammatory Diseases
p38 Mitogen-Activated Protein Kinases / metabolism

Substances

Cell Adhesion Molecules
DICAM protein, mouse
p38 Mitogen-Activated Protein Kinases

Grants and funding

This research was supported by the National Research Foundation of Korea (NRF) grant, funded by the Korean government (Ministry of Science and ICT) (grant numbers NRF-2020R1A2C1004517) (NRF-2020R1F1A1075199).