TCRζ mRNA splice variant forms observed in the peripheral blood T cells from systemic lupus erythematosus patients

Kensei Tsuzaka, Kyoko Nozaki, Chika Kumazawa, Kiyono Shiraishi, Yumiko Setoyama, Keiko Yoshimoto, Tohru Abe, Tsutomus Takeuchi

Research output: Contribution to journalReview article

9 Citations (Scopus)

Abstract

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease of unknown etiology. Tyrosine phosphorylation and protein expression of the T-cell receptor ζ chain (ζ) have been reported to be significantly decreased in SLE T cells. In addition, ζ mRNA with alternatively spliced 3′ untranslated region (ζmRNA/as-3′UTR) is detected predominantly in SLE T cells, and aberrant ζ mRNA accompanied by the mutations in the open reading frame including ζ mRNA lacking exon7 (ζmRNA/exon7-) is observed in SLE T cells. These ζ mRNA splice variant forms exhibit a reduction in the expression of TCR/CD3 complex and ζ protein on their cell surface due to the instability of ζ mRNA splice variant forms as well as the reduction in interleukin (IL)-2 production after stimulating with anti-CD3 antibody. Data from cDNA microarray showed that 36 genes encoding cytokines and chemokines, including IL-2, IL-15, IL-18, and TGF-β2, were down-regulated in the MA5.8 cells transfected with the ζ mRNA splice variant forms. Another 16 genes were up-regulated and included genes associated with membranous proteins and cell damage granules, including the genes encoding poliovirus-receptor-related 2, syndecan-1, and granzyme A.

Original languageEnglish
Pages (from-to)185-193
Number of pages9
JournalSpringer Seminars in Immunopathology
Volume28
Issue number2
DOIs
Publication statusPublished - 2006 Oct 1
Externally publishedYes

ASJC Scopus subject areas

  • Immunology

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