title: Loss of Murine FOXO3 in Cells of the Myeloid Lineage Enhances Myelopoiesis but Protects from K/BxN-Serum Transfer-Induced Arthritis.
abstract: FOXO transcription factors have a highly conserved role in regulating transcription of genes involved in differentiation, cell cycle arrest, apoptosis and DNA repair. Loss of FOXO3 in mice has previously been shown to result in a myeloproliferative disease. In agreement with this, we found that an independent Foxo3 null mouse strain, Foxo3Kca, exhibits an increase in neutrophils in the spleen, bone marrow and blood. This coincides with an expansion of myeloid progenitor cells including pre-granulocyte-macrophage progenitors (Pre-GMs) and granulocyte-macrophage progenitors (GMPs). Surprisingly, despite neutrophilia, the severity of passive serum transfer arthritis was markedly attenuated in Foxo3Kca mice. These defects appear to be at least partially intrinsic to the myeloid lineage, as deleting Foxo3 specifically from myeloid cells using LysMCre also leads to an elevated number of neutrophils and protection from K/BxN-serum transfer-induced arthritis.
authors.affiliation: Molecular Biology Section, Division of Biological Science, University of California San Diego, La Jolla, California, United States of America; Department of Cellular and Molecular Medicine, University of California San Diego, La Jolla, California, United States of America.
authors.forename: Hannah
authors.initials: H
authors.lastname: Kang
authors.affiliation: Department of Medicine, School of Medicine, University of California San Diego, La Jolla, California, United States of America.
authors.forename: Maripat
authors.initials: M
authors.lastname: Corr
authors.affiliation: Molecular Biology Section, Division of Biological Science, University of California San Diego, La Jolla, California, United States of America; Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Robert
authors.initials: R
authors.lastname: Mansson
authors.affiliation: Molecular Biology Section, Division of Biological Science, University of California San Diego, La Jolla, California, United States of America.
authors.forename: Eva
authors.initials: E
authors.lastname: Welinder
authors.affiliation: Molecular Biology Section, Division of Biological Science, University of California San Diego, La Jolla, California, United States of America; Department of Cellular and Molecular Medicine, University of California San Diego, La Jolla, California, United States of America.
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Hedrick
authors.affiliation: Department of Cellular and Molecular Medicine, University of California San Diego, La Jolla, California, United States of America.
authors.forename: Erica L
authors.initials: EL
authors.lastname: Stone
mesh_terms: D000818:Animals; D001168:Arthritis / Q000235:genetics / Q000276:immunology*; D004198:Disease Susceptibility; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors / Q000235:genetics* / Q000378:metabolism; D006706:Homeostasis; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D023461:Myeloid Progenitor Cells / Q000502:physiology*; D038042:Myelopoiesis; D009504:Neutrophils / Q000502:physiology; D010538:Peritonitis / Q000276:immunology
chemical_list: D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors; C474033:FoxO3 protein, mouse