Phosphorylated ERM is responsible for increased T cell polarization, adhesion, and migration in patients with systemic lupus erythematosus.
Systemic lupus erythematosus (SLE) is an autoimmune/inflammatory disease characterized by autoantibody production and abnormal T cells that infiltrate tissues through not well-known mechanisms. We report that SLE T lymphocytes display increased levels of CD44, ezrin, radixin, and moesin (ERM) phosphorylation, stronger actin polymerization, higher polar cap formation, and enhanced adhesion and chemotactic migration compared with T cells from patients with rheumatoid arthritis and normal individuals. Silencing of CD44 by CD44 small interfering RNA in SLE T cells inhibited significantly their ability to adhere and migrate as did treatment with Rho kinase and actin polymerization inhibitors. Forced expression of T567D-ezrin, a phosphorylation-mimic form, enhanced remarkably the adhesion and migration rate of normal T cells. Anti-CD3/TCR autoantibodies present in SLE sera caused increased ERM phosphorylation, adhesion, and migration in normal T cells. pERM and CD44 are highly expressed in T cells infiltrating in the kidneys of patients with lupus nephritis. These data prove that increased ERM phosphorylation represents a key molecular abnormality that guides T cell adhesion and migration in SLE patients.
Li
Yansong
Y
Department of Cellular Injury, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA.
Harada
Tatsuhiro
T
Juang
Yuang-Taung
YT
Kyttaris
Vasileios C
VC
Wang
Ying
Y
Zidanic
Michael
M
Tung
Kenneth
K
Tsokos
George C
GC
D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid; D002448:Cell Adhesion; D016764:Cell Polarity; D002634:Chemotaxis, Leukocyte; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D005260:Female; D006801:Humans; D018960:Hyaluronan Receptors; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D008181:Lupus Nephritis / Q000276:immunology; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D008840:Microfilament Proteins / Q000378:metabolism; D008875:Middle Aged; D010766:Phosphorylation; D013601:T-Lymphocytes / Q000166:cytology*; D000099149:Ezrin
D003598:Cytoskeletal Proteins; D018960:Hyaluronan Receptors; D008565:Membrane Proteins; D008840:Microfilament Proteins; D000099149:Ezrin; C071058:moesin; C071776:radixin