The miR-181 family regulates colonic inflammation through its activity in the intestinal epithelium.

Autor:	Jimenez MT; Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA.; Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA., Clark ML; Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA.; Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA., Wright JM; Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA.; Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA., Michieletto MF; Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA.; Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA., Liu S; Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA.; Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA., Erickson I; Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA.; Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA., Dohnalova L; Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA.; Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA., Uhr GT; Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA.; Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA., Tello-Cajiao J; Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA.; Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA., Joannas L; Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA.; Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA., Williams A; Division of Allergy and Immunology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL., Gagliani N; Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.; Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.; Immunology and Allergy Unit, Department of Medicine, Solna, Karolinska Institute and University Hospital, Stockholm, Sweden., Bewtra M; Department of Medicine, Division of Gastroenterology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA.; Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania, Philadelphia, PA.; Department of Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, PA., Tomov VT; Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA.; Department of Medicine, Division of Gastroenterology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA., Thaiss CA; Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA.; Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA., Henao-Mejia J; Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA.; Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA.; Division of Protective Immunity, Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, University of Pennsylvania, Philadelphia, PA.
Jazyk:	angličtina
Zdroj:	The Journal of experimental medicine [J Exp Med] 2022 Dec 05; Vol. 219 (12). Date of Electronic Publication: 2022 Sep 08.
DOI:	10.1084/jem.20212278
Abstrakt:	The intestinal epithelium is a key physical interface that integrates dietary and microbial signals to regulate nutrient uptake and mucosal immune cell function. The transcriptional programs that regulate intestinal epithelial cell (IEC) quiescence, proliferation, and differentiation have been well characterized. However, how gene expression networks critical for IECs are posttranscriptionally regulated during homeostasis or inflammatory disease remains poorly understood. Herein, we show that a conserved family of microRNAs, miR-181, is significantly downregulated in IECs from patients with inflammatory bowel disease and mice with chemical-induced colitis. Strikingly, we showed that miR-181 expression within IECs, but not the hematopoietic system, is required for protection against severe colonic inflammation in response to epithelial injury in mice. Mechanistically, we showed that miR-181 expression increases the proliferative capacity of IECs, likely through the regulation of Wnt signaling, independently of the gut microbiota composition. As epithelial reconstitution is crucial to restore intestinal homeostasis after injury, the miR-181 family represents a potential therapeutic target against severe intestinal inflammation. (© 2022 Jimenez et al.)
Databáze:	MEDLINE
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