TY - JOUR
T1 - Perivascular localization of macrophages in the intestinal mucosa is regulated by Nr4a1 and the microbiome
AU - Honda, Masaki
AU - Surewaard, Bas G.J.
AU - Watanabe, Mayuki
AU - Hedrick, Catherine C.
AU - Lee, Woo Yong
AU - Brown, Kirsty
AU - McCoy, Kathy D.
AU - Kubes, Paul
N1 - Funding Information:
We thank Trecia Nussbaumer for mice husbandry. We thank Karen Poon from the Snyder Institute Molecular Core for assistance with flow cytometry. This work is supported in part by the International Microbiome Centre (IMC) funded through the Cumming School of Medicine, University of Calgary, Western Economic Diversification (WED) and Alberta Economic Development and Trade (AEDT), Canada. M.H. is supported by the Research Fellowship of the Uehara Memorial Foundation and grants from the Ministry of Education, Culture, Sports, Sciences and Technology of Japan (KAKENHI 19H03716). M.W. is supported by the Postdoctoral Fellowship of the Uehara Memorial Foundation. B.G.S. is supported by the Canadian Institutes of Health Research (CIHR). P.K.’s laboratory is supported by a foundation grant from the CIHR, Alberta Innovates Health Solutions, the Heart and Stroke Foundation of Canada and the Canada Research Chairs program.
Publisher Copyright:
© 2020, Crown.
PY - 2020/12/1
Y1 - 2020/12/1
N2 - While the ontogeny and recruitment of the intestinal monocyte/macrophage lineage has been studied extensively, their precise localization and function has been overlooked. Here we show by imaging the murine small and large intestines in steady-state that intestinal CX3CR1+ macrophages form an interdigitated network intimately adherent to the entire mucosal lamina propria vasculature. The macrophages form contacts with each other, which are disrupted in the absence of microbiome, monocyte recruitment (Ccr2−/−), or monocyte conversion (Nr4a1−/−). In dysbiosis, gaps exist between the perivascular macrophages correlating with increased bacterial translocation from the lamina propria into the bloodstream. The recruitment of monocytes and conversion to macrophages during intestinal injury is also dependent upon CCR2, Nr4a1 and the microbiome. These findings demonstrate a relationship between microbiome and the maturation of lamina propria perivascular macrophages into a tight anatomical barrier that might function to prevent bacterial translocation. These cells are also critical for emergency vascular repair.
AB - While the ontogeny and recruitment of the intestinal monocyte/macrophage lineage has been studied extensively, their precise localization and function has been overlooked. Here we show by imaging the murine small and large intestines in steady-state that intestinal CX3CR1+ macrophages form an interdigitated network intimately adherent to the entire mucosal lamina propria vasculature. The macrophages form contacts with each other, which are disrupted in the absence of microbiome, monocyte recruitment (Ccr2−/−), or monocyte conversion (Nr4a1−/−). In dysbiosis, gaps exist between the perivascular macrophages correlating with increased bacterial translocation from the lamina propria into the bloodstream. The recruitment of monocytes and conversion to macrophages during intestinal injury is also dependent upon CCR2, Nr4a1 and the microbiome. These findings demonstrate a relationship between microbiome and the maturation of lamina propria perivascular macrophages into a tight anatomical barrier that might function to prevent bacterial translocation. These cells are also critical for emergency vascular repair.
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U2 - 10.1038/s41467-020-15068-4
DO - 10.1038/s41467-020-15068-4
M3 - Article
C2 - 32165624
AN - SCOPUS:85081585702
SN - 2041-1723
VL - 11
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 1329
ER -