Aggravation of lipopolysaccharide-induced depressive-like behavior in CCR4-deficient mice

Yuta Hara; Tatsuma Honzawa; Moeka Kitagawa; Ritsuki Sano; Kazuhiko Matsuo; Takashi Nakayama

doi:10.1016/j.jphs.2023.08.003

Aggravation of lipopolysaccharide-induced depressive-like behavior in CCR4-deficient mice

J Pharmacol Sci. 2023 Nov;153(3):89-93. doi: 10.1016/j.jphs.2023.08.003. Epub 2023 Aug 24.

Authors

Yuta Hara¹, Tatsuma Honzawa¹, Moeka Kitagawa¹, Ritsuki Sano¹, Kazuhiko Matsuo¹, Takashi Nakayama²

Affiliations

¹ Division of Chemotherapy, Kindai University Faculty of Pharmacy, Higashi-osaka, Osaka, Japan.
² Division of Chemotherapy, Kindai University Faculty of Pharmacy, Higashi-osaka, Osaka, Japan. Electronic address: nakayama@phar.kindai.ac.jp.

PMID: 37770160
DOI: 10.1016/j.jphs.2023.08.003

Abstract

Increasing evidence indicates that immune abnormalities are associated with the pathogenesis of depression. CCR4 is a chemokine receptor that regulates regulatory T cell (Treg) and Th17 cell migration. Here, using a lipopolysaccharide (LPS)-induced depression mouse model, we demonstrated that CCR4 deficiency exacerbated depressive-like behavior. Tregs and M2 macrophages, but not Th17 cells, were decreased in the brain of CCR4-deficient mice. Consistently, treatment with a CCR4 inhibitor reduced Tregs and M2 macrophages in the brain and exacerbated depressive-like behavior. Thus, CCR4 may contribute to the reduction of depressive symptoms by promoting Treg recruitment to the brain and subsequent M2 macrophage polarization.

Keywords: CCR4; Depression; Treg.