WNT2B Deficiency Causes Enhanced Susceptibility to Colitis Due to Increased Inflammatory Cytokine Production.

Autor:	O'Connell AE; Division of Newborn Medicine, Boston Children's Hospital, Boston, Massachusetts; The Manton Center for Orphan Disease Research at Boston Children's Hospital, Boston, Massachusetts; Department of Pediatrics, Harvard Medical School, Boston, Massachusetts. Electronic address: amy.oconnell@childrens.harvard.edu., Raveenthiraraj S; Division of Newborn Medicine, Boston Children's Hospital, Boston, Massachusetts., Oliveira LFS; Division of Newborn Medicine, Boston Children's Hospital, Boston, Massachusetts., Adegboye C; Division of Newborn Medicine, Boston Children's Hospital, Boston, Massachusetts., Dasuri VS; Division of Newborn Medicine, Boston Children's Hospital, Boston, Massachusetts., Qi W; Division of Endocrinology, Boston Children's Hospital, Boston, Massachusetts., Khetani RS; Harvard T.H. Chan School of Public Health, Boston, Massachusetts., Singh A; Department of Pediatric, General, and Thoracic Surgery, Cincinnati Children's Hospital, Cincinnati, Ohio; Center for Stem Cell and Organoid Medicine, Cincinnati Children's Hospital, Cincinnati, Ohio., Sundaram N; Department of Pediatric, General, and Thoracic Surgery, Cincinnati Children's Hospital, Cincinnati, Ohio; Center for Stem Cell and Organoid Medicine, Cincinnati Children's Hospital, Cincinnati, Ohio., Lin J; Division of Genetics and Genomics, Boston Children's Hospital, Boston, Massachusetts., Nandivada P; Department of Surgery, Boston Children's Hospital, Boston, Massachusetts., Rincón-Cruz L; Department of Surgery, Boston Children's Hospital, Boston, Massachusetts., Goldsmith JD; Department of Pathology, Boston Children's Hospital, Boston, Massachusetts., Thiagarajah JR; Department of Pediatrics, Harvard Medical School, Boston, Massachusetts; Division of Gastroenterology, Boston Children's Hospital, Boston, Massachusetts., Carlone DL; Department of Pediatrics, Harvard Medical School, Boston, Massachusetts; Division of Endocrinology, Boston Children's Hospital, Boston, Massachusetts; Harvard Stem Cell Institute, Cambridge, Massachusetts., Turner JR; Laboratory of Mucosal Barrier Pathobiology, Department of Pathology and Medicine, Brigham & Women's Hospital and Harvard Medical School, Boston, Massachusetts., Agrawal PB; Division of Newborn Medicine, Boston Children's Hospital, Boston, Massachusetts; The Manton Center for Orphan Disease Research at Boston Children's Hospital, Boston, Massachusetts; Department of Pediatrics, Harvard Medical School, Boston, Massachusetts; Division of Genetics and Genomics, Boston Children's Hospital, Boston, Massachusetts; Division of Neonatology, Department of Pediatrics, University of Miami Miller School of Medicine and Holtz Children's Hospital, Jackson Health System, Miami, Florida., Helmrath M; Department of Pediatric, General, and Thoracic Surgery, Cincinnati Children's Hospital, Cincinnati, Ohio; Center for Stem Cell and Organoid Medicine, Cincinnati Children's Hospital, Cincinnati, Ohio., Breault DT; Department of Pediatrics, Harvard Medical School, Boston, Massachusetts; Division of Endocrinology, Boston Children's Hospital, Boston, Massachusetts; Harvard Stem Cell Institute, Cambridge, Massachusetts.
Jazyk:	angličtina
Zdroj:	Cellular and molecular gastroenterology and hepatology [Cell Mol Gastroenterol Hepatol] 2024; Vol. 18 (2), pp. 101349. Date of Electronic Publication: 2024 Apr 30.
DOI:	10.1016/j.jcmgh.2024.04.006
Abstrakt:	Background & Aims: Humans with WNT2B deficiency have severe intestinal disease, including significant inflammatory injury, highlighting a critical role for WNT2B. We sought to understand how WNT2B contributes to intestinal homeostasis. Methods: We investigated the intestinal health of Wnt2b knock out (KO) mice. We assessed the baseline histology and health of the small intestine and colon, and the impact of inflammatory challenge using dextran sodium sulfate (DSS). We also evaluated human intestinal tissue. Results: Mice with WNT2B deficiency had normal baseline histology but enhanced susceptibility to DSS colitis because of an increased early injury response. Although intestinal stem cells markers were decreased, epithelial proliferation was similar to control subjects. Wnt2b KO mice showed an enhanced inflammatory signature after DSS treatment. Wnt2b KO colon and human WNT2B-deficient organoids had increased levels of CXCR4 and IL6, and biopsy tissue from humans showed increased neutrophils. Conclusions: WNT2B is important for regulation of inflammation in the intestine. Absence of WNT2B leads to increased expression of inflammatory cytokines and increased susceptibility to gastrointestinal inflammation, particularly in the colon. (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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