title: Intestinal CD169(+) macrophages initiate mucosal inflammation by secreting CCL8 that recruits inflammatory monocytes.
abstract: Lamina propria (LP) macrophages are constantly exposed to commensal bacteria, and are refractory to those antigens in an interleukin (IL)-10-dependent fashion. However, the mechanisms that discriminate hazardous invasion by bacteria from peaceful co-existence with them remain elusive. Here we show that CD169(+) macrophages reside not at the villus tip, but at the bottom-end of the LP microenvironment. Following mucosal injury, the CD169(+) macrophages recruit inflammatory monocytes by secreting CCL8. Selective depletion of CD169(+) macrophages or administration of neutralizing anti-CCL8 antibody ameliorates the symptoms of experimentally induced colitis in mice. Collectively, we identify an LP-resident macrophage subset that links mucosal damage and inflammatory monocyte recruitment. Our results suggest that CD169(+) macrophage-derived CCL8 serves as an emergency alert for the collapse of barrier defence, and is a promising target for the suppression of mucosal injury.
authors.affiliation: 1] Laboratory of Immune regulation, School of Life Science, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan [2] Japan Science and Technology Agency, PRESTO, 4-1-8 Honcho, Kawaguchi, Saitama 332-0012, Japan.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Asano
authors.affiliation: Laboratory of Immune regulation, School of Life Science, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan.
authors.forename: Naomichi
authors.initials: N
authors.lastname: Takahashi
authors.affiliation: Laboratory of Immune regulation, School of Life Science, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan.
authors.forename: Mikiko
authors.initials: M
authors.lastname: Ushiki
authors.affiliation: Laboratory of Immune regulation, School of Life Science, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan.
authors.forename: Misa
authors.initials: M
authors.lastname: Monya
authors.affiliation: Laboratory of Immune regulation, School of Life Science, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan.
authors.forename: Fumiaki
authors.initials: F
authors.lastname: Aihara
authors.affiliation: Laboratory of Immune regulation, School of Life Science, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan.
authors.forename: Erika
authors.initials: E
authors.lastname: Kuboki
authors.affiliation: Laboratory of Immune regulation, School of Life Science, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan.
authors.forename: Shigetaka
authors.initials: S
authors.lastname: Moriyama
authors.affiliation: Laboratory of Immune regulation, School of Life Science, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan.
authors.forename: Mayumi
authors.initials: M
authors.lastname: Iida
authors.affiliation: Laboratory of Veterinary Physiology, School of Veterinary Medicine, Rakuno Gakuen University, 582 Bunkyodai-Midorimachi, Ebetsu, Hokkaido 069-8501, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kitamura
authors.affiliation: Institute of Cell Biology, Shandong University School of Medicine, PO Box 73, No. 44 Wenhua Xi Road, Jinan, Shandong 250012, China.
authors.forename: Chun-Hong
authors.initials: CH
authors.lastname: Qiu
authors.affiliation: Immunogenomics Laboratory, RIKEN Center for Integrated Medical Sciences, 1-7-22 Suehirocho, Tsurumi, Yokohama 227-0045, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Watanabe
authors.affiliation: Laboratory of Immune regulation, School of Life Science, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Tanaka
mesh_terms: D000818:Animals; D054412:Chemokine CCL8 / Q000378:metabolism*; D003092:Colitis / Q000139:chemically induced / Q000276:immunology*; D003106:Colon / Q000276:immunology*; D016264:Dextran Sulfate; D005260:Female; D018928:Immunity, Mucosal; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D009000:Monocytes / Q000502:physiology*; D009092:Mucous Membrane / Q000276:immunology; D063267:Sialic Acid Binding Ig-like Lectin 1 / Q000378:metabolism
chemical_list: C515454:Ccl8 protein, mouse; D054412:Chemokine CCL8; D063267:Sialic Acid Binding Ig-like Lectin 1; C571167:Siglec1 protein, mouse; D016264:Dextran Sulfate