期刊
JOURNAL OF IMMUNOLOGY
卷 181, 期 5, 页码 3658-3664出版社
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.181.5.3658
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资金
- National Institutes of Health [R01AI42269, R01AI49954, R01AI068787]
T cells from patients with systemic lupus erythematosus are characterized by decreased expression of CD3 zeta-chain and increased expression of FcR gamma-chain, which becomes part of the CD3 complex and contributes to aberrant signaling. Elf-1 enhances the expression of CD3, whereas it suppresses the expression of FcR gamma gene and lupus T cells have decreased amounts of DNA-binding 98 kDa form of Elf-1. We show that the aberrantly increased PP2A in lupus T cells dephosphorylates; Elf-1 at Thr-231. Dephosphorylation results in limited expression and binding of the 98 kDa Elf-1 form to the CD3 zeta and FcR gamma promoters. Suppression of the expression of the PP2A leads to increased expression of CD3 zeta and decreased expression of FcR gamma genes and correction of the early signaling response. Therefore, PP2A serves as a central determinant of abnormal T cell function in human lupus and may represent an appropriate treatment target.
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