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

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 t...

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Autores principales: Asano, Kenichi, Takahashi, Naomichi, Ushiki, Mikiko, Monya, Misa, Aihara, Fumiaki, Kuboki, Erika, Moriyama, Shigetaka, Iida, Mayumi, Kitamura, Hiroshi, Qiu, Chun-Hong, Watanabe, Takashi, Tanaka, Masato
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Pub. Group 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4518321/
https://www.ncbi.nlm.nih.gov/pubmed/26193821
http://dx.doi.org/10.1038/ncomms8802
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author Asano, Kenichi
Takahashi, Naomichi
Ushiki, Mikiko
Monya, Misa
Aihara, Fumiaki
Kuboki, Erika
Moriyama, Shigetaka
Iida, Mayumi
Kitamura, Hiroshi
Qiu, Chun-Hong
Watanabe, Takashi
Tanaka, Masato
author_facet Asano, Kenichi
Takahashi, Naomichi
Ushiki, Mikiko
Monya, Misa
Aihara, Fumiaki
Kuboki, Erika
Moriyama, Shigetaka
Iida, Mayumi
Kitamura, Hiroshi
Qiu, Chun-Hong
Watanabe, Takashi
Tanaka, Masato
author_sort Asano, Kenichi
collection PubMed
description 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.
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spelling pubmed-45183212015-08-07 Intestinal CD169(+) macrophages initiate mucosal inflammation by secreting CCL8 that recruits inflammatory monocytes Asano, Kenichi Takahashi, Naomichi Ushiki, Mikiko Monya, Misa Aihara, Fumiaki Kuboki, Erika Moriyama, Shigetaka Iida, Mayumi Kitamura, Hiroshi Qiu, Chun-Hong Watanabe, Takashi Tanaka, Masato Nat Commun Article 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 Pub. Group 2015-07-21 /pmc/articles/PMC4518321/ /pubmed/26193821 http://dx.doi.org/10.1038/ncomms8802 Text en Copyright © 2015, Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved. http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Asano, Kenichi
Takahashi, Naomichi
Ushiki, Mikiko
Monya, Misa
Aihara, Fumiaki
Kuboki, Erika
Moriyama, Shigetaka
Iida, Mayumi
Kitamura, Hiroshi
Qiu, Chun-Hong
Watanabe, Takashi
Tanaka, Masato
Intestinal CD169(+) macrophages initiate mucosal inflammation by secreting CCL8 that recruits inflammatory monocytes
title Intestinal CD169(+) macrophages initiate mucosal inflammation by secreting CCL8 that recruits inflammatory monocytes
title_full Intestinal CD169(+) macrophages initiate mucosal inflammation by secreting CCL8 that recruits inflammatory monocytes
title_fullStr Intestinal CD169(+) macrophages initiate mucosal inflammation by secreting CCL8 that recruits inflammatory monocytes
title_full_unstemmed Intestinal CD169(+) macrophages initiate mucosal inflammation by secreting CCL8 that recruits inflammatory monocytes
title_short Intestinal CD169(+) macrophages initiate mucosal inflammation by secreting CCL8 that recruits inflammatory monocytes
title_sort intestinal cd169(+) macrophages initiate mucosal inflammation by secreting ccl8 that recruits inflammatory monocytes
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4518321/
https://www.ncbi.nlm.nih.gov/pubmed/26193821
http://dx.doi.org/10.1038/ncomms8802
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