The miR-181 family regulates colonic inflammation through its activity in the intestinal epithelium
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The miR-181 family regulates colonic inflammation through its activity in the intestinal epithelium. / Jimenez, Monica T; Clark, Megan L; Wright, Jasmine M; Michieletto, Michaël F; Liu, Suying; Erickson, Isabel; Dohnalova, Lenka; Uhr, Giulia T; Tello-Cajiao, John; Joannas, Leonel; Williams, Adam; Gagliani, Nicola; Bewtra, Meenakshi; Tomov, Vesselin T; Thaiss, Christoph A; Henao-Mejia, Jorge.
in: J EXP MED, Jahrgang 219, Nr. 12, e20212278, 05.12.2022.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - The miR-181 family regulates colonic inflammation through its activity in the intestinal epithelium
AU - Jimenez, Monica T
AU - Clark, Megan L
AU - Wright, Jasmine M
AU - Michieletto, Michaël F
AU - Liu, Suying
AU - Erickson, Isabel
AU - Dohnalova, Lenka
AU - Uhr, Giulia T
AU - Tello-Cajiao, John
AU - Joannas, Leonel
AU - Williams, Adam
AU - Gagliani, Nicola
AU - Bewtra, Meenakshi
AU - Tomov, Vesselin T
AU - Thaiss, Christoph A
AU - Henao-Mejia, Jorge
N1 - © 2022 Jimenez et al.
PY - 2022/12/5
Y1 - 2022/12/5
N2 - 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.
AB - 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.
KW - Animals
KW - Colitis/chemically induced
KW - Epithelial Cells/metabolism
KW - Inflammation/genetics
KW - Intestinal Mucosa
KW - Mice
KW - MicroRNAs/genetics
U2 - 10.1084/jem.20212278
DO - 10.1084/jem.20212278
M3 - SCORING: Journal article
C2 - 36074090
VL - 219
JO - J EXP MED
JF - J EXP MED
SN - 0022-1007
IS - 12
M1 - e20212278
ER -