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

Division of Rheumatology, Department of Internal Medicine, Saitama Medical Center, Saitama Medical University, 1981 Kamoda, Kawagoe, Saitama, 350-8550, Japan.
Springer Seminars in Immunopathology (Impact Factor: 4.17). 11/2006; 28(2):185-93. DOI: 10.1007/s00281-006-0035-2
Source: PubMed

ABSTRACT Systemic lupus erythematosus (SLE) is a systemic autoimmune disease of unknown etiology. Tyrosine phosphorylation and protein expression of the T-cell receptor zeta chain (zeta) have been reported to be significantly decreased in SLE T cells. In addition, zeta mRNA with alternatively spliced 3' untranslated region (zetamRNA/as-3'UTR) is detected predominantly in SLE T cells, and aberrant zeta mRNA accompanied by the mutations in the open reading frame including zeta mRNA lacking exon7 (zetamRNA/exon7-) is observed in SLE T cells. These zeta mRNA splice variant forms exhibit a reduction in the expression of TCR/CD3 complex and zeta protein on their cell surface due to the instability of zeta 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-beta2, were down-regulated in the MA5.8 cells transfected with the zeta 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.

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