title: Decreased secretion of Paneth cell α-defensins in graft-versus-host disease.
abstract: BACKGROUND
  Intestinal microbial ecology is actively regulated by Paneth cell-derived antimicrobial peptides, α-defensins. Graft-versus-host disease (GVHD) is a major complication of allogeneic hematopoietic stem cell transplantation (SCT). We previously demonstrated that Paneth cells are targeted by GVHD, and their expression of antimicrobial peptide α-defensins is impaired, leading to a loss of physiological diversity among the microflora and development of bloodstream infection. Herein, we evaluated whether fecal levels of α-defensins could be surrogate marker of intestinal dysbiosis.
  
  
  METHODS
  We directly measured α-defensin cryptdin-1 (Crp1) in fecal pellets of mice with GVHD by using a novel enzyme-linked immunosorbent assay.
  
  
  RESULTS
  Fecal levels of Crp1 were significantly decreased in mice with GVHD but unchanged in mice without GVHD after SCT. These were correlated with intestinal flora diversity.
  
  
  CONCLUSIONS
  We demonstrate a link between reduced secretion of Paneth cell α-defensins and dysbiosis of intestinal flora in GVHD. Fecal levels of α-defensins could be surrogate markers for intestinal microbial homeostasis.
authors.affiliation: Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Science, Fukuoka, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Eriguchi
authors.affiliation: Department of Cell Biological Science, Graduate School of Life Science, Faculty of Advanced Life Science, Hokkaido University, Sapporo, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Nakamura
authors.affiliation: Department of Hematology, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors.forename: D
authors.initials: D
authors.lastname: Hashimoto
authors.affiliation: Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Science, Fukuoka, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Shimoda
authors.affiliation: Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Science, Fukuoka, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Shimono
authors.affiliation: Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Science, Fukuoka, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Akashi
authors.affiliation: Department of Cell Biological Science, Graduate School of Life Science, Faculty of Advanced Life Science, Hokkaido University, Sapporo, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Ayabe
authors.affiliation: Department of Hematology, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Teshima
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D064806:Dysbiosis / Q000378:metabolism* / Q000382:microbiology; D004797:Enzyme-Linked Immunosorbent Assay; D005243:Feces / Q000737:chemistry* / Q000382:microbiology; D005260:Female; D000069196:Gastrointestinal Microbiome; D006086:Graft vs Host Disease / Q000378:metabolism*; D018380:Hematopoietic Stem Cell Transplantation; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000382:microbiology; D060588:LIM Domain Proteins / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D009687:Nuclear Proteins / Q000378:metabolism*; D019879:Paneth Cells / Q000378:metabolism*; D014184:Transplantation, Homologous; D023084:alpha-Defensins / Q000378:metabolism*
chemical_list: D015415:Biomarkers; C486177:Csrp1 protein, mouse; D060588:LIM Domain Proteins; D009687:Nuclear Proteins; D023084:alpha-Defensins
keywords: Paneth cells; cryptdin; fecal testing; graft-versus-host disease; hematopoietic stem cell transplantation; microbiota; mouse model; α-defensins