Decreased DAP12 expression in natural killer lymphocytes from patients with systemic lupus erythematosus is associated with increased transcript mutations.
Decreased numbers of natural killer (NK) cells and impaired NK function have been reported in patients with systemic lupus erythematosus (SLE). Since DAP12 plays a pivotal role in activation of NK cells, we analyzed the expressions of DAP12 protein and mRNA in peripheral blood NK cells from patients with SLE. Both DAP12 protein and mRNA expressions in NK cells from the SLE patients were decreased compared with those in NK cells from normal subjects. Sequence analysis of DAP12 cDNA showed increased nucleotide mutations, including both nucleotide substitutions and deletions. In spite of the mRNA mutations, we found no mutations in genomic DNA, suggesting that mRNA was modified during or after transcription. Decreased expression of DAP12 in NK cells from the patients was accompanied by increased expression of ADAR1 (adenosine deaminase that acts on RNA transcripts) and by decreased expression of NKp44. These results suggest that abnormal expression of DAP12 molecules in NK cells may account for the impairment of NK cell function in patients with SLE.
Toyabe
Shin-ichi
S
Division of Pediatrics, Department of Homeostatic Regulation and Development, Niigata Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-dori, Niigata City 951-8510, Japan. toyabe@med.niigata-u.ac.jp
Kaneko
Utako
U
Uchiyama
Makoto
M
D048868:Adaptor Proteins, Signal Transducing; D000243:Adenosine Deaminase / Q000235:genetics / Q000502:physiology; D000293:Adolescent; D015536:Down-Regulation; D005260:Female; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology*; D008180:Lupus Erythematosus, Systemic / Q000235:genetics* / Q000276:immunology*; D008565:Membrane Proteins; D009154:Mutation / Q000235:genetics*; D055629:Natural Cytotoxicity Triggering Receptor 2; D017393:RNA Editing / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D016601:RNA-Binding Proteins; D011971:Receptors, Immunologic / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D017422:Sequence Analysis, DNA; D014158:Transcription, Genetic; D015854:Up-Regulation
D048868:Adaptor Proteins, Signal Transducing; D008565:Membrane Proteins; C112837:NCR2 protein, human; D055629:Natural Cytotoxicity Triggering Receptor 2; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D011971:Receptors, Immunologic; C110546:TYROBP protein, human; C567955:ADARB1 protein, human; D000243:Adenosine Deaminase