New Paper: Perivascular Localization of Macrophages in the Intestinal Mucosa is Regulated by Nr4a1 and the Microbiome

Congratulations to IMPACTT Director and Platform 1 Lead Dr. Kathy McCoy, as well as Platform 1 Co-Lead Dr. Paul Kubes, on this recent publication!

Fig 3. Gut microbiota affects the distribution and morphology of intestinal CX3CR1+ macrophages from the article: Perivascular localization of macrophages in the intestinal mucosa is regulated by Nr4a1 and the microbiome.
Gut microbiota affects the distribution and morphology of intestinal CX3CR1+ macrophages. Source data are provided as a Source Data file. (Copyright: https://creativecommons.org/licenses/by/4.0/)

Abstract

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.

Publication: Perivascular localization of macrophages in the intestinal mucosa is regulated by Nr4a1 and the microbiome. Honda M, Surewaard BGJ, Watanabe M, Hendrick CC, Lee WY, Brown K, McCoy KD, Kubes P. Nature Communications. 12 March 2020. Congratulations!