title: Microbiota and caspase-1/caspase-8 regulate IL-1β-mediated bone disease.
abstract: A leucine-to-proline missense mutation at residue 98 in the proline-serine-threonine phosphatase interacting protein 2 (Pstpip2) gene leads to autoinflammatory disease that is characterized by splenomegaly, necrosis, and spontaneous development of osteomyelitis in mice (Pstpip2cmo). Disease progression in these mice resembles that of chronic recurrent multifocal osteomyelitis in humans. Our group and others have shown that disease progression in Pstpip2cmomice is mediated by the cytokine IL-1β, independently of inflammasomes or IL-1α. Our recent publication highlighted herein establishes that diet-induced changes in intestinal microbiota provide protection against the development of osteomyelitis in Pstpip2cmomice. Moreover, the proteases caspase-1 and caspase-8 have redundant roles in cleaving IL-1β and promoting disease. This addendum reviews the current literature on the Pstpip2cmomurine disease model and the clinical significance of the role of PSTPIP2 in regulating autoinflammatory osteomyelitis, which is mediated by innate components of immune cells.
authors.affiliation: a Department of Immunology , St. Jude Children's Research Hospital , Memphis , TN , USA.
authors.forename: Farrah C
authors.initials: FC
authors.lastname: Phillips
authors.affiliation: a Department of Immunology , St. Jude Children's Research Hospital , Memphis , TN , USA.
authors.forename: Prajwal
authors.initials: P
authors.lastname: Gurung
authors.affiliation: a Department of Immunology , St. Jude Children's Research Hospital , Memphis , TN , USA.
authors.forename: Thirumala-Devi
authors.initials: TD
authors.lastname: Kanneganti
mesh_terms: D000818:Animals; D020170:Caspase 1 / Q000235:genetics / Q000276:immunology*; D053181:Caspase 8 / Q000235:genetics / Q000276:immunology*; D018450:Disease Progression; D000069196:Gastrointestinal Microbiome; D006801:Humans; D053583:Interleukin-1beta / Q000235:genetics / Q000276:immunology*; D010019:Osteomyelitis / Q000201:enzymology / Q000235:genetics / Q000276:immunology* / Q000382:microbiology*
chemical_list: D053583:Interleukin-1beta; D053181:Caspase 8; D020170:Caspase 1
keywords: IL-1beta; Pstpip2; autoinflammatory; caspase; high-fat diet; microbiota; neutrophil; osteomyelitis