TCRζ mRNA with an alternatively spliced 3′-untranslated region detected in systemic lupus erythematosus patients leads to the down-regulation of TCRζ and TCR/CD3 complex

Kensei Tsuzaka, Izumi Fukuhara, Yumiko Setoyama, Keiko Yoshimoto, Katsuya Suzuki, Tohru Abe, Tsutomu Takeuchi

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Abstract

The reduction or absence of TCR ζ-chain (ζ) expression in systemic lupus erythematosus (SLE) patients is thought to be related to the pathogenesis of SLE. Recently, we reported the predominant expression of ζ mRNA containing an alternatively spliced 3′-untranslated region (3′UTR; ζmRNA/as-3′UTR) and a reduction in the expression of ζ mRNA containing the wild-type 3′UTR (ζmRNA/w-3′UTR) in T cells from SLE patients. Here we show that AS3′UTR mutants (MA5.8 cells deficient in ζ protein that have been transfected with ζmRNA/as-3′UTR) exhibit a reduction in the expression of TCR/CD3 complex and ζ protein on their cell surface as well as a reduction in the production of IL-2 after stimulation with anti-CD3 Ab compared with that in wild-type 3′UTR mutants (MA5.8 cells transfected with ζmRNA/w-3′UTR). Furthermore, the real-time PCR analyses demonstrated that the half-life of ζmRNA/as-3′UTR in AS3′UTR mutants (3 h) was much shorter than that of ζmRNA/w-3′UTR in wild-type 3′UTR mutants (15 h). Thus, the lower stability of ζmRNA/as-3′UTR, which is predominant in SLE T cells, may be responsible for the reduced expression of the TCR/CD3 complex, including ζ protein, in SLE T cells.

Original languageEnglish
Pages (from-to)2496-2503
Number of pages8
JournalJournal of Immunology
Volume171
Issue number5
Publication statusPublished - 2003 Sep 1
Externally publishedYes

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T-Cell Antigen Receptor-CD3 Complex
3' Untranslated Regions
Systemic Lupus Erythematosus
Down-Regulation
Messenger RNA
T-Lymphocytes
Proteins
RNA Stability
Interleukin-2
Half-Life
Real-Time Polymerase Chain Reaction

ASJC Scopus subject areas

  • Immunology

Cite this

TCRζ mRNA with an alternatively spliced 3′-untranslated region detected in systemic lupus erythematosus patients leads to the down-regulation of TCRζ and TCR/CD3 complex. / Tsuzaka, Kensei; Fukuhara, Izumi; Setoyama, Yumiko; Yoshimoto, Keiko; Suzuki, Katsuya; Abe, Tohru; Takeuchi, Tsutomu.

In: Journal of Immunology, Vol. 171, No. 5, 01.09.2003, p. 2496-2503.

Research output: Contribution to journalArticle

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abstract = "The reduction or absence of TCR ζ-chain (ζ) expression in systemic lupus erythematosus (SLE) patients is thought to be related to the pathogenesis of SLE. Recently, we reported the predominant expression of ζ mRNA containing an alternatively spliced 3′-untranslated region (3′UTR; ζmRNA/as-3′UTR) and a reduction in the expression of ζ mRNA containing the wild-type 3′UTR (ζmRNA/w-3′UTR) in T cells from SLE patients. Here we show that AS3′UTR mutants (MA5.8 cells deficient in ζ protein that have been transfected with ζmRNA/as-3′UTR) exhibit a reduction in the expression of TCR/CD3 complex and ζ protein on their cell surface as well as a reduction in the production of IL-2 after stimulation with anti-CD3 Ab compared with that in wild-type 3′UTR mutants (MA5.8 cells transfected with ζmRNA/w-3′UTR). Furthermore, the real-time PCR analyses demonstrated that the half-life of ζmRNA/as-3′UTR in AS3′UTR mutants (3 h) was much shorter than that of ζmRNA/w-3′UTR in wild-type 3′UTR mutants (15 h). Thus, the lower stability of ζmRNA/as-3′UTR, which is predominant in SLE T cells, may be responsible for the reduced expression of the TCR/CD3 complex, including ζ protein, in SLE T cells.",
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AU - Setoyama, Yumiko

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AU - Abe, Tohru

AU - Takeuchi, Tsutomu

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