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Microbiota-derived butyrate restricts tuft cell differentiation via histone deacetylase 3 to modulate intestinal type 2 immunity.
Eshleman, Emily M; Rice, Taylor; Potter, Crystal; Waddell, Amanda; Hashimoto-Hill, Seika; Woo, Vivienne; Field, Sydney; Engleman, Laura; Lim, Hee-Woong; Schumacher, Michael A; Frey, Mark R; Denson, Lee A; Finkelman, Fred D; Alenghat, Theresa.
Affiliation
  • Eshleman EM; Division of Immunobiology, Cincinnati Children's Hospital Medical Center and Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA; Center for Inflammation and Tolerance, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
  • Rice T; Division of Immunobiology, Cincinnati Children's Hospital Medical Center and Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA; Center for Inflammation and Tolerance, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
  • Potter C; Division of Immunobiology, Cincinnati Children's Hospital Medical Center and Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA; Division of Immunology, Allergy and Rheumatology, Department of Internal Medicine, University of Cincinnati College of Medicine, C
  • Waddell A; Division of Immunobiology, Cincinnati Children's Hospital Medical Center and Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA; Center for Inflammation and Tolerance, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
  • Hashimoto-Hill S; Division of Immunobiology, Cincinnati Children's Hospital Medical Center and Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA; Center for Inflammation and Tolerance, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
  • Woo V; Division of Immunobiology, Cincinnati Children's Hospital Medical Center and Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA; Center for Inflammation and Tolerance, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
  • Field S; Division of Immunobiology, Cincinnati Children's Hospital Medical Center and Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
  • Engleman L; Division of Immunobiology, Cincinnati Children's Hospital Medical Center and Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA; Center for Inflammation and Tolerance, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
  • Lim HW; Division of Biomedical Informatics, Cincinnati Children's Hospital Medical Center and Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
  • Schumacher MA; The Saban Research Institute, Children's Hospital Los Angeles, Los Angeles, CA, USA; Department of Pediatrics and Department of Biochemistry and Molecular Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
  • Frey MR; The Saban Research Institute, Children's Hospital Los Angeles, Los Angeles, CA, USA; Department of Pediatrics and Department of Biochemistry and Molecular Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
  • Denson LA; Division of Gastroenterology, Hepatology, and Nutrition, Cincinnati Children's Hospital Medical Center and Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
  • Finkelman FD; Division of Immunobiology, Cincinnati Children's Hospital Medical Center and Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA; Division of Immunology, Allergy and Rheumatology, Department of Internal Medicine, University of Cincinnati College of Medicine, C
  • Alenghat T; Division of Immunobiology, Cincinnati Children's Hospital Medical Center and Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA; Center for Inflammation and Tolerance, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA. Electronic address: the
Immunity ; 57(2): 319-332.e6, 2024 Feb 13.
Article in En | MEDLINE | ID: mdl-38295798
ABSTRACT
Tuft cells in mucosal tissues are key regulators of type 2 immunity. Here, we examined the impact of the microbiota on tuft cell biology in the intestine. Succinate induction of tuft cells and type 2 innate lymphoid cells was elevated with loss of gut microbiota. Colonization with butyrate-producing bacteria or treatment with butyrate suppressed this effect and reduced intestinal histone deacetylase activity. Epithelial-intrinsic deletion of the epigenetic-modifying enzyme histone deacetylase 3 (HDAC3) inhibited tuft cell expansion in vivo and impaired type 2 immune responses during helminth infection. Butyrate restricted stem cell differentiation into tuft cells, and inhibition of HDAC3 in adult mice and human intestinal organoids blocked tuft cell expansion. Collectively, these data define a HDAC3 mechanism in stem cells for tuft cell differentiation that is dampened by a commensal metabolite, revealing a pathway whereby the microbiota calibrate intestinal type 2 immunity.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Microbiota / Intestinal Mucosa Limits: Adult / Animals / Humans Language: En Journal: Immunity Journal subject: ALERGIA E IMUNOLOGIA Year: 2024 Type: Article Affiliation country: United States
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Microbiota / Intestinal Mucosa Limits: Adult / Animals / Humans Language: En Journal: Immunity Journal subject: ALERGIA E IMUNOLOGIA Year: 2024 Type: Article Affiliation country: United States