title: Boosting Apoptotic Cell Clearance by Colonic Epithelial Cells Attenuates Inflammation In Vivo.
abstract: Few apoptotic corpses are seen even in tissues with high cellular turnover, leading to the notion that the capacity for engulfment in vivo is vast. Whether corpse clearance can be enhanced in vivo for potential benefit is not known. In a colonic inflammation model, we noted that the expression of the phagocytic receptor Bai1 was progressively downmodulated. Consistent with this, BAI1-deficient mice had more pronounced colitis and lower survival, with many uncleared apoptotic corpses and inflammatory cytokines within the colonic epithelium. When we engineered and tested transgenic mice overexpressing BAI1, these had fewer apoptotic cells, reduced inflammation, and attenuated disease. Boosting BAI1-mediated uptake by intestinal epithelial cells (rather than myeloid cells) was important in attenuating inflammation. A signaling-deficient BAI1 transgene could not provide a similar benefit. Collectively, these complementary genetic approaches showed that cell clearance could be boosted in vivo, with potential to regulate tissue inflammation in specific contexts.
authors.affiliation: Department of Microbiology, Immunology, Cancer Biology, University of Virginia, Charlottesville, VA 22908, USA; Beirne B. Carter Center for Immunology Research, University of Virginia, Charlottesville, VA 22908, USA; Center for Cell Clearance, University of Virginia, Charlottesville, VA 22908, USA.
authors.forename: Chang Sup
authors.initials: CS
authors.lastname: Lee
authors.affiliation: Department of Microbiology, Immunology, Cancer Biology, University of Virginia, Charlottesville, VA 22908, USA; Beirne B. Carter Center for Immunology Research, University of Virginia, Charlottesville, VA 22908, USA; Center for Cell Clearance, University of Virginia, Charlottesville, VA 22908, USA.
authors.forename: Kristen K
authors.initials: KK
authors.lastname: Penberthy
authors.affiliation: Department of Urology, University of Virginia, Charlottesville, VA 22908, USA.
authors.forename: Karen M
authors.initials: KM
authors.lastname: Wheeler
authors.affiliation: Department of Microbiology, Immunology, Cancer Biology, University of Virginia, Charlottesville, VA 22908, USA; Beirne B. Carter Center for Immunology Research, University of Virginia, Charlottesville, VA 22908, USA; Center for Cell Clearance, University of Virginia, Charlottesville, VA 22908, USA.
authors.forename: Ignacio J
authors.initials: IJ
authors.lastname: Juncadella
authors.affiliation: Molecular Signaling and Cell Death Unit, Inflammation Research Center (IRC), VIB, 9052 Ghent, Belgium; The Department of Biomedical Molecular Biology, University of Ghent, 9052 Ghent, Belgium; Methusalem Program, University of Ghent, 9052 Ghent, Belgium.
authors.forename: Peter
authors.initials: P
authors.lastname: Vandenabeele
authors.affiliation: Department of Urology, University of Virginia, Charlottesville, VA 22908, USA.
authors.forename: Jeffrey J
authors.initials: JJ
authors.lastname: Lysiak
authors.affiliation: Department of Microbiology, Immunology, Cancer Biology, University of Virginia, Charlottesville, VA 22908, USA; Beirne B. Carter Center for Immunology Research, University of Virginia, Charlottesville, VA 22908, USA; Center for Cell Clearance, University of Virginia, Charlottesville, VA 22908, USA. Electronic address: ravi@virginia.edu.
authors.forename: Kodi S
authors.initials: KS
authors.lastname: Ravichandran
mesh_terms: D042501:Angiogenic Proteins / Q000235:genetics*; D000818:Animals; D017209:Apoptosis / Q000276:immunology*; D045744:Cell Line, Tumor; D003092:Colitis / Q000139:chemically induced / Q000276:immunology*; D003106:Colon / Q000276:immunology / Q000473:pathology; D016207:Cytokines / Q000276:immunology; D016264:Dextran Sulfate; D004847:Epithelial Cells / Q000276:immunology*; D045325:HCT116 Cells; D006801:Humans; D007249:Inflammation / Q000276:immunology; D007413:Intestinal Mucosa / Q000166:cytology / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D015398:Signal Transduction / Q000276:immunology
chemical_list: C524949:Adgrb1 protein, mouse; D042501:Angiogenic Proteins; D016207:Cytokines; D034741:RNA, Small Interfering; D016264:Dextran Sulfate