Selected Publication:

SHR Neuro Cancer Cardio Lipid Metab Microb

Fritsch, SD; Sukhbaatar, N; Gonzales, K; Sahu, A; Tran, L; Vogel, A; Mazic, M; Wilson, JL; Forisch, S; Mayr, H; Oberle, R; Weiszmann, J; Brenner, M; Vanhoutte, R; Hofmann, M; Pirnes-Karhu, S; Magnes, C; Kuehnast, T; Weckwerth, W; Bock, C; Klavins, K; Hengstschläger, M; Moissl-Eichinger, C; Schabbauer, G; Egger, G; Pirinen, E; Verhelst, SHL; Weichhart, T.
Metabolic support by macrophages sustains colonic epithelial homeostasis
CELL METAB. 2023; 35(11): 1931-+. Doi: 10.1016/j.cmet.2023.09.010
Web of Science PubMed FullText FullText_MUG

 

Co-authors Med Uni Graz

Kühnast Torben Wilhelm

Moissl-Eichinger Christine

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Abstract:

The intestinal epithelium has a high turnover rate and constantly renews itself through proliferation of intestinal crypt cells, which depends on insufficiently characterized signals from the microenvironment. Here, we showed that colonic macrophages were located directly adjacent to epithelial crypt cells in mice, where they metabolically supported epithelial cell proliferation in an mTORC1-dependent manner. Specifically, deletion of tuberous sclerosis complex 2 (Tsc2) in macrophages activated mTORC1 signaling that protected against colitis-induced intestinal damage and induced the synthesis of the polyamines spermidine and spermine. Epithelial cells ingested these polyamines and rewired their cellular metabolism to optimize proliferation and defense. Notably, spermine directly stimulated proliferation of colon epithelial cells and colon organoids. Genetic interference with polyamine production in macrophages altered global polyamine levels in the colon and modified epithelial cell proliferation. Our results suggest that macrophages act as "commensals"that provide metabolic support to promote efficient self-renewal of the colon epithelium.

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