Intestinal CD169^+ macrophages initiate mucosal inflammation by secreting CCL8 that recruits inflammatory monocytes
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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.
- Nature Communications
Nature Communications (6), 7802-1-7802-14, 2015-07
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