FoxO3a involved in neutrophil and T cell survival is overexpressed in rheumatoid blood and synovial tissue.
OBJECTIVE
FoxO3a is a transcriptional factor implicated in cell cycle regulation and apoptosis. Since rheumatoid arthritis (RA) is associated with apoptosis defects, the expression level, regulation and phosphorylation status of FoxO3a was investigated in blood and synovium from patients with RA.


METHODS
In microarray experiments, an overexpression of FoxO3a mRNA was observed in blood from patients with RA compared with healthy controls. FoxO3a mRNA expression was quantified in polymorphonuclear cells (PMNs) and peripheral blood mononuclear cells from patients with RA by qRT-PCR. Total FoxO3a and phosphorylated FoxO3a (pFoxO3a) protein expression was analysed in blood leucocytes from patients with RA versus controls and in synovium from patients with RA versus patients with osteoarthritis (OA) by immunostaining.


RESULTS
FoxO3a mRNA and protein expression levels were increased in blood from patients with RA compared with controls. FoxO3a overexpression was primarily observed in PMNs. In synovium from patients with RA, both total and inactive phosphorylated FoxO3a proteins were detected. FoxO3a was detected primarily in the sublining T lymphocytes of synovium from patients with RA compared with the lining layer tissue from patients with RA and OA, underlying a role for FoxO3a proteins in inflammation in RA.


CONCLUSIONS
The overexpression of FoxO3a in blood from patients with RA, particularly in PMNs, suggests a potential role for this gene in the pathogenesis of RA through increased survival of blood PMNs. In synovium from patients with RA, FoxO3a mainly detected in inflammatory aggregates may also regulate the chronic survival of T lymphocytes.
Clinical Immunology Unit, Department of Immunology and Rheumatology, Joint Unit Hospices Civils de Lyon-bioMérieux, Hôpital Edouard Herriot, 5 place d'Arsonval, Lyon, France.
Fanny
F
Turrel-Davin
Anne
A
Tournadre
Alexandre
A
Pachot
Béatrice
B
Arnaud
Marie-Angélique
MA
Cazalis
Bruno
B
Mougin
Pierre
P
Miossec
D000328:Adult; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000378:metabolism*; D002470:Cell Survival; D005260:Female; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000378:metabolism*; D010003:Osteoarthritis / Q000378:metabolism; D010766:Phosphorylation; D012333:RNA, Messenger / Q000235:genetics; D013583:Synovial Membrane / Q000378:metabolism*; D013601:T-Lymphocytes / Q000378:metabolism*
C499517:FOXO3 protein, human; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors; D012333:RNA, Messenger