Intestinal CD169(+) macrophages initiate mucosal inflammation by secreting CCL8 that recruits inflammatory monocytes.

Kenichi Asano, Naomichi Takahashi, Mikiko Ushiki, Misa Monya, Fumiaki Aihara, Erika Kuboki, Shigetaka Moriyama, Mayumi Iida, Hiroshi Kitamura, Chun-Hong Qiu, Takashi Watanabe, Masato Tanaka

Index: Nat. Commun. 6 , 7802, (2015)

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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.