Intestinal epithelial c-Maf expression determines enterocyte differentiation and nutrient uptake in mice.

Autor:	Cosovanu C; Department of Microbiology, Infectious Diseases and Immunology, Charité - Universitätsmedizin Berlin, Berlin, Germany., Resch P; Department of Microbiology, Infectious Diseases and Immunology, Charité - Universitätsmedizin Berlin, Berlin, Germany., Jordan S; Department of Microbiology, Infectious Diseases and Immunology, Charité - Universitätsmedizin Berlin, Berlin, Germany., Lehmann A; Department of Biochemistry, Charité - Universitätsmedizin Berlin, Berlin, Germany., Ralser M; Department of Biochemistry, Charité - Universitätsmedizin Berlin, Berlin, Germany.; The Francis Crick Institute, Molecular Biology of Metabolism Laboratory, London, UK., Farztdinov V; Core Facility - High-Throughput Mass Spectrometry, Charité - Universitätsmedizin Berlin, Berlin, Germany., Spranger J; Department of Endocrinology and Metabolism, Charité - Universitätsmedizin Berlin, Berlin, Germany.; German Centre for Cardiovascular Research, partner site Berlin, Berlin, Germany., Mülleder M; Core Facility - High-Throughput Mass Spectrometry, Charité - Universitätsmedizin Berlin, Berlin, Germany., Brachs S; Department of Endocrinology and Metabolism, Charité - Universitätsmedizin Berlin, Berlin, Germany.; German Centre for Cardiovascular Research, partner site Berlin, Berlin, Germany., Neumann C; Department of Microbiology, Infectious Diseases and Immunology, Charité - Universitätsmedizin Berlin, Berlin, Germany.
Jazyk:	angličtina
Zdroj:	The Journal of experimental medicine [J Exp Med] 2022 Dec 05; Vol. 219 (12). Date of Electronic Publication: 2022 Sep 19.
DOI:	10.1084/jem.20220233
Abstrakt:	The primary function of the small intestine (SI) is to absorb nutrients to maintain whole-body energy homeostasis. Enterocytes are the major epithelial cell type facilitating nutrient sensing and uptake. However, the molecular regulators governing enterocytes have remained undefined. Here, we identify c-Maf as an enterocyte-specific transcription factor within the SI epithelium. c-Maf expression was determined by opposing Noggin/BMP signals and overlapped with the zonated enrichment of nutrient transporters in the mid-villus region. Functionally, enterocytes required c-Maf to appropriately differentiate along the villus axis. Specifically, gene programs controlling carbohydrate and protein absorption were c-Maf-dependent. Consequently, epithelial cell-specific c-Maf deletion resulted in impaired enterocyte maturation and nutrient uptake, including defects in the adaptation to different nutrient availability. Concomitantly, intraepithelial lymphocytes were less abundant, while commensal epithelial cell-attaching SFB overgrew in a c-Maf-deficient environment, highlighting the close interdependence between the intestinal epithelium, immune system, and microbiota. Collectively, our data identified c-Maf as a key regulator of SI enterocyte differentiation and function, essential for nutrient, immune, and microbial homeostasis. (© 2022 Cosovanu et al.)
Databáze:	MEDLINE
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