The DEK nuclear autoantigen is a secreted chemotactic factor.
The nuclear DNA-binding protein DEK is an autoantigen that has been implicated in the regulation of transcription, chromatin architecture, and mRNA processing. We demonstrate here that DEK is actively secreted by macrophages and is also found in synovial fluid samples from patients with juvenile arthritis. Secretion of DEK is modulated by casein kinase 2, stimulated by interleukin-8, and inhibited by dexamethasone and cyclosporine A, consistent with a role as a proinflammatory molecule. DEK is secreted in both a free form and in exosomes, vesicular structures in which transcription-modulating factors such as DEK have not previously been found. Furthermore, DEK functions as a chemotactic factor, attracting neutrophils, CD8+ T lymphocytes, and natural killer cells. Therefore, the DEK autoantigen, previously described as a strictly nuclear protein, is secreted and can act as an extracellular chemoattractant, suggesting a direct role for DEK in inflammation.
Mor-Vaknin
Nirit
N
Department of Internal Medicine, Division of Infectious Diseases, University of Michigan Medical Center, Ann Arbor, MI 48109-0640, USA.
Punturieri
Antonello
A
Sitwala
Kajal
K
Faulkner
Neil
N
Legendre
Maureen
M
Khodadoust
Michael S
MS
Kappes
Ferdinand
F
Ruth
Jeffrey H
JH
Koch
Alisa
A
Glass
David
D
Petruzzelli
Lilli
L
Adams
Barbara S
BS
Markovitz
David M
DM
D001171:Arthritis, Juvenile / Q000276:immunology / Q000378:metabolism* / Q000473:pathology*; D001324:Autoantigens / Q000378:metabolism / Q000502:physiology*; D002478:Cells, Cultured; D002630:Chemotactic Factors / Q000378:metabolism* / Q000502:physiology; D002634:Chemotaxis, Leukocyte; D002648:Child; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism* / Q000502:physiology; D045604:Extracellular Fluid / Q000276:immunology / Q000378:metabolism; D006801:Humans; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D009000:Monocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D015513:Oncogene Proteins / Q000378:metabolism* / Q000502:physiology; D000075223:Poly-ADP-Ribose Binding Proteins
D001324:Autoantigens; D002630:Chemotactic Factors; D002868:Chromosomal Proteins, Non-Histone; C084738:DEK protein, human; D015513:Oncogene Proteins; D000075223:Poly-ADP-Ribose Binding Proteins