CCR4 and CCR5 Involvement in Monocyte-Derived Macrophage Migration in Neuroinflammation

• Published in: Frontiers in immunology Vol. 13; p. 876033
• Main Authors: Kim, Jong Youl, Kim, Jiwon, Huang, Meiying, Kosonen, Renée, Lee, Jong Eun
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 12-05-2022
• Subjects: Animals; CCR4; CCR5; Chemokines - metabolism; Disease Models, Animal; Immunology; Lipopolysaccharides; Macrophages - metabolism; microglia; monocyte-derived macrophage; neuroinflammation; Neuroinflammatory Diseases; Stroke; monocyte-derived macrophage; CCR5; neuroinflammation; CCR4; microglia
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2022.876033

Microglia, resident macrophages in the brain, play major roles in neuroinflammation after an acute many neurological diseases, including stroke. Our recent animal stroke model showed that interleukin (IL)-4 and IL-13 released by microglia are converted into monocyte-derived macrophages. However, the correlation with the migration mechanism of these cells is still unclear. This study aimed to clarify the effect of these cells on their migration and to identify potential targets that influence neuroinflammatory conditions. Inflammatory conditions were induced by lipopolysaccharide (LPS) treatment in
and
models. Cell migration was observed using transwell assay, and target chemokines were screened using the proteome profiler array in the
model. Intravital, IVIS, and CLARITY imaging were used in the
model. After LPS (1 ng/ml) treatment in BV2 (microglia cell line) and J774 (monocyte/macrophage cell line) cells, BV2 migration was approximately two-fold more enhanced compared to J774 migration. Overall, six types of chemokine C-C motif ligands (CCLs) were detected from the BV2 conditioned medium with LPS. These CCLs were related to C-C motif receptor (CCR)4 and CCR5. In the
model, CCR4 and CCR5 antagonist significantly inhibited the migration of monocyte-derived macrophages to brain tissue following LPS (5 µg) treatment. In conclusion, the chemokines released by microglia may influence migration of monocyte-derived macrophages in necroinflammation conditions inducted by microglial activation. CCR4 and CCR5 expressed on monocyte-derived macrophages interacted with these chemokines and induced migration. Therefore, CCR4 and CCR5 may be explored as new therapeutic targets for neuroinflammation.