Limits...
Loss of Murine FOXO3 in Cells of the Myeloid Lineage Enhances Myelopoiesis but Protects from K/BxN-Serum Transfer-Induced Arthritis.

Kang H, Corr M, Mansson R, Welinder E, Hedrick SM, Stone EL - PLoS ONE (2015)

Bottom Line: In agreement with this, we found that an independent Foxo3 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).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.

View Article: PubMed Central - PubMed

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.

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 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.

No MeSH data available.


Related in: MedlinePlus

Foxo3Kca mice exhibit reduced severity of arthritis.WT and Foxo3Kca mice were injected i.p. with K/BxN sera on d 0 and d 2 and ankle thickness and clinical scores were determined in blinded fashion. Graphs show the ankle thickening of WT or Foxo3Kca mice (Left) or clinical index of paws (Right). Data are representative of at least three independent experiments with at least six paws (for ankle thickening) or 3 mice (for clinical index) per group.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4430473&req=5

pone.0126728.g004: Foxo3Kca mice exhibit reduced severity of arthritis.WT and Foxo3Kca mice were injected i.p. with K/BxN sera on d 0 and d 2 and ankle thickness and clinical scores were determined in blinded fashion. Graphs show the ankle thickening of WT or Foxo3Kca mice (Left) or clinical index of paws (Right). Data are representative of at least three independent experiments with at least six paws (for ankle thickening) or 3 mice (for clinical index) per group.

Mentions: Neutrophils are essential for the effector phase of passive K/BxN-serum transfer arthritis [19, 20]. In this model sera from K/BxN mice containing IgG specific for the glycolytic enzyme glucose-6-phosphate isomerase are injected into mice to initiate disease [21–23]. Foxo3Trap mutant mice were found to be resistant to this model of arthritis, and this was attributed to increased apoptosis of Foxo3Trap neutrophils during inflammation [8]. Therefore, we wished to determine if Foxo3Kca mice normally develop K/BxN-serum transfer arthritis. WT and Foxo3Kca mice were injected i.p. with K/BxN sera on d 0 and d 2 and the progression of arthritis was observed. In WT mice ankle thickening and clinical signs of inflammation were evident by d 3 and remained elevated for more than 2 weeks (Fig 4). However, Foxo3Kca mice were relatively protected from paw swelling and clinical signs of inflammation induced by K/BxN sera (Fig 4).


Loss of Murine FOXO3 in Cells of the Myeloid Lineage Enhances Myelopoiesis but Protects from K/BxN-Serum Transfer-Induced Arthritis.

Kang H, Corr M, Mansson R, Welinder E, Hedrick SM, Stone EL - PLoS ONE (2015)

Foxo3Kca mice exhibit reduced severity of arthritis.WT and Foxo3Kca mice were injected i.p. with K/BxN sera on d 0 and d 2 and ankle thickness and clinical scores were determined in blinded fashion. Graphs show the ankle thickening of WT or Foxo3Kca mice (Left) or clinical index of paws (Right). Data are representative of at least three independent experiments with at least six paws (for ankle thickening) or 3 mice (for clinical index) per group.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4430473&req=5

pone.0126728.g004: Foxo3Kca mice exhibit reduced severity of arthritis.WT and Foxo3Kca mice were injected i.p. with K/BxN sera on d 0 and d 2 and ankle thickness and clinical scores were determined in blinded fashion. Graphs show the ankle thickening of WT or Foxo3Kca mice (Left) or clinical index of paws (Right). Data are representative of at least three independent experiments with at least six paws (for ankle thickening) or 3 mice (for clinical index) per group.
Mentions: Neutrophils are essential for the effector phase of passive K/BxN-serum transfer arthritis [19, 20]. In this model sera from K/BxN mice containing IgG specific for the glycolytic enzyme glucose-6-phosphate isomerase are injected into mice to initiate disease [21–23]. Foxo3Trap mutant mice were found to be resistant to this model of arthritis, and this was attributed to increased apoptosis of Foxo3Trap neutrophils during inflammation [8]. Therefore, we wished to determine if Foxo3Kca mice normally develop K/BxN-serum transfer arthritis. WT and Foxo3Kca mice were injected i.p. with K/BxN sera on d 0 and d 2 and the progression of arthritis was observed. In WT mice ankle thickening and clinical signs of inflammation were evident by d 3 and remained elevated for more than 2 weeks (Fig 4). However, Foxo3Kca mice were relatively protected from paw swelling and clinical signs of inflammation induced by K/BxN sera (Fig 4).

Bottom Line: In agreement with this, we found that an independent Foxo3 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).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.

View Article: PubMed Central - PubMed

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.

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 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.

No MeSH data available.


Related in: MedlinePlus