Enteric glia regulate Paneth cell secretion and intestinal microbial ecology.

Autor:	Prochera A; Division of Gastroenterology, Department of Pediatrics, Boston Children's Hospital and Harvard Medical School, 300 Longwood Ave, Boston, MA 02115, USA., Muppirala AN; Division of Gastroenterology, Department of Pediatrics, Boston Children's Hospital and Harvard Medical School, 300 Longwood Ave, Boston, MA 02115, USA., Kuziel GA; Division of Gastroenterology, Department of Pediatrics, Boston Children's Hospital and Harvard Medical School, 300 Longwood Ave, Boston, MA 02115, USA.; Division of Infectious Diseases, Department of Pediatrics, Boston Children's Hospital and Harvard Medical School, 300 Longwood Ave, Boston, MA 02115, USA.; Department of Microbiology, Harvard Medical School, Boston, MA 02115, USA., Soualhi S; Division of Gastroenterology, Department of Pediatrics, Boston Children's Hospital and Harvard Medical School, 300 Longwood Ave, Boston, MA 02115, USA., Shepherd A; Division of Gastroenterology, Department of Pediatrics, Boston Children's Hospital and Harvard Medical School, 300 Longwood Ave, Boston, MA 02115, USA., Sun L; Research Computing, Department of Information Technology, Boston Children's Hospital, 300 Longwood Ave, Boston, MA 02115, USA., Issac B; Research Computing, Department of Information Technology, Boston Children's Hospital, 300 Longwood Ave, Boston, MA 02115, USA., Rosenberg HJ; Division of Gastroenterology, Department of Pediatrics, Boston Children's Hospital and Harvard Medical School, 300 Longwood Ave, Boston, MA 02115, USA.; Department of Pathology, Beth Israel Deaconess Medical Center, Boston, MA, USA., Karim F; Institute of Human Nutrition, Columbia University Irving Medical Center, New York, NY, USA., Perez K; Division of Gastroenterology, Department of Pediatrics, Boston Children's Hospital and Harvard Medical School, 300 Longwood Ave, Boston, MA 02115, USA., Smith KH; Department of Surgery, Beth Israel Deaconess Medical Center, Boston, MA, USA., Archibald TH; Department of Pathology, Beth Israel Deaconess Medical Center, Boston, MA, USA., Rakoff-Nahoum S; Division of Gastroenterology, Department of Pediatrics, Boston Children's Hospital and Harvard Medical School, 300 Longwood Ave, Boston, MA 02115, USA.; Division of Infectious Diseases, Department of Pediatrics, Boston Children's Hospital and Harvard Medical School, 300 Longwood Ave, Boston, MA 02115, USA.; Department of Microbiology, Harvard Medical School, Boston, MA 02115, USA., Hagen SJ; Department of Surgery, Beth Israel Deaconess Medical Center, Boston, MA, USA., Rao M; Division of Gastroenterology, Department of Pediatrics, Boston Children's Hospital and Harvard Medical School, 300 Longwood Ave, Boston, MA 02115, USA.
Jazyk:	angličtina
Zdroj:	BioRxiv : the preprint server for biology [bioRxiv] 2024 Apr 19. Date of Electronic Publication: 2024 Apr 19.
DOI:	10.1101/2024.04.15.589545
Abstrakt:	Glial cells of the enteric nervous system (ENS) interact closely with the intestinal epithelium and secrete signals that influence epithelial cell proliferation and barrier formation in vitro . Whether these interactions are important in vivo, however, is unclear because previous studies reached conflicting conclusions [1]. To better define the roles of enteric glia in steady state regulation of the intestinal epithelium, we characterized the glia in closest proximity to epithelial cells and found that the majority express PLP1 in both mice and humans. To test their functions using an unbiased approach, we genetically depleted PLP1 + cells in mice and transcriptionally profiled the small and large intestines. Surprisingly, glial loss had minimal effects on transcriptional programs and the few identified changes varied along the gastrointestinal tract. In the ileum, where enteric glia had been considered most essential for epithelial integrity, glial depletion did not drastically alter epithelial gene expression but caused a modest enrichment in signatures of Paneth cells, a secretory cell type important for innate immunity. In the absence of PLP1 + glia, Paneth cell number was intact, but a subset appeared abnormal with irregular and heterogenous cytoplasmic granules, suggesting a secretory deficit. Consistent with this possibility, ileal explants from glial-depleted mice secreted less functional lysozyme than controls with corresponding effects on fecal microbial composition. Collectively, these data suggest that enteric glia do not exert broad effects on the intestinal epithelium but have an essential role in regulating Paneth cell function and gut microbial ecology.
Databáze:	MEDLINE
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