title: A signalling cascade of IL-33 to IL-13 regulates metaplasia in the mouse stomach.
abstract: Alternatively activated macrophages (M2) are associated with the progression of spasmolytic polypeptide-expressing metaplasia (SPEM) in the stomach. However, the precise mechanism(s) and critical mediators that induce SPEM are unknown.
  
  
  
  To determine candidate genes important in these processes, macrophages from the stomach corpus of mice with SPEM (DMP-777-treated) or advanced SPEM (L635-treated) were isolated and RNA sequenced. Effects on metaplasia development after acute parietal cell loss induced by L635 were evaluated in interleukin (IL)-33, IL-33 receptor (ST2) and IL-13 knockout (KO) mice.
  
  
  
  Profiling of metaplasia-associated macrophages in the stomach identified an M2a-polarised macrophage population. Expression of IL-33 was significantly upregulated in macrophages associated with advanced SPEM. L635 induced metaplasia in the stomachs of wild-type mice, but not in the stomachs of IL-33 and ST2 KO mice. While IL-5 and IL-9 were not required for metaplasia induction, IL-13 KO mice did not develop metaplasia in response to L635. Administration of IL-13 to ST2 KO mice re-established the induction of metaplasia following acute parietal cell loss.
  
  
  
  Metaplasia induction and macrophage polarisation after parietal cell loss is coordinated through a cytokine signalling network of IL-33 and IL-13, linking a combined response to injury by both intrinsic mucosal mechanisms and infiltrating M2 macrophages.
authors.affiliation: Departments of Cell and Developmental Biology, Vanderbilt University, Nashville, Tennessee, USA.|Epithelial Biology Center, Vanderbilt University, Nashville, Tennessee, USA.
authors.forename: Christine P
authors.initials: CP
authors.lastname: Petersen
authors.affiliation: Departments of Cell and Developmental Biology, Vanderbilt University, Nashville, Tennessee, USA.|Epithelial Biology Center, Vanderbilt University, Nashville, Tennessee, USA.
authors.forename: Anne R
authors.initials: AR
authors.lastname: Meyer
authors.affiliation: Department of Pathology, Case Western Reserve School of Medicine, Cleveland, Ohio, USA.
authors.forename: Carlo
authors.initials: C
authors.lastname: De Salvo
authors.affiliation: Epithelial Biology Center, Vanderbilt University, Nashville, Tennessee, USA.|Nashville VA Medical Center, Vanderbilt University, Nashville, Tennessee, USA.|Department of Surgery, Vanderbilt University, Nashville, Tennessee, USA.
authors.forename: Eunyoung
authors.initials: E
authors.lastname: Choi
authors.affiliation: Epithelial Biology Center, Vanderbilt University, Nashville, Tennessee, USA.|Department of Surgery, Vanderbilt University, Nashville, Tennessee, USA.
authors.forename: Cameron
authors.initials: C
authors.lastname: Schlegel
authors.affiliation: Epithelial Biology Center, Vanderbilt University, Nashville, Tennessee, USA.
authors.forename: Alec
authors.initials: A
authors.lastname: Petersen
authors.affiliation: Epithelial Biology Center, Vanderbilt University, Nashville, Tennessee, USA.|Department of Surgery, Vanderbilt University, Nashville, Tennessee, USA.
authors.forename: Amy C
authors.initials: AC
authors.lastname: Engevik
authors.affiliation: HudsonAlpha Institute for Biotechnology, Huntsville, Alabama, USA.
authors.forename: Nripesh
authors.initials: N
authors.lastname: Prasad
authors.affiliation: HudsonAlpha Institute for Biotechnology, Huntsville, Alabama, USA.
authors.forename: Shawn E
authors.initials: SE
authors.lastname: Levy
authors.affiliation: Department of Medicine, Vanderbilt University, Nashville, Tennessee, USA.
authors.forename: R Stokes
authors.initials: RS
authors.lastname: Peebles
authors.affiliation: Department of Pathology, Case Western Reserve School of Medicine, Cleveland, Ohio, USA.
authors.forename: Theresa T
authors.initials: TT
authors.lastname: Pizarro
authors.affiliation: Departments of Cell and Developmental Biology, Vanderbilt University, Nashville, Tennessee, USA.|Epithelial Biology Center, Vanderbilt University, Nashville, Tennessee, USA.|Nashville VA Medical Center, Vanderbilt University, Nashville, Tennessee, USA.|Department of Surgery, Vanderbilt University, Nashville, Tennessee, USA.
authors.forename: James R
authors.initials: JR
authors.lastname: Goldenring
mesh_terms: D000818:Animals; D005434:Flow Cytometry; D005753:Gastric Mucosa / Q000378:metabolism; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins; D000072179:Interleukin-1 Receptor-Like 1 Protein; D018793:Interleukin-13 / Q000235:genetics / Q000378:metabolism*; D000067596:Interleukin-33 / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism*; D008679:Metaplasia / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010295:Parietal Cells, Gastric / Q000166:cytology; D010455:Peptides / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D018123:Receptors, Interleukin / Q000235:genetics; D015398:Signal Transduction; D013270:Stomach / Q000166:cytology*
chemical_list: C486189:Il1rl1 protein, mouse; D036341:Intercellular Signaling Peptides and Proteins; D000072179:Interleukin-1 Receptor-Like 1 Protein; D018793:Interleukin-13; D000067596:Interleukin-33; D010455:Peptides; D018123:Receptors, Interleukin; C451060:spasmolytic polypeptide
keywords: CELLULAR IMMUNOLOGY; CYTOKINES; GASTRIC PRE-CANCER; GASTRITIS; MACROPHAGES