A role for Fli-1 in B cell proliferation : implications for SLE pathogenesis
Transgenic overexpression of Fli-1 in normal mice leads to SLE-like disease and increased expression was reported in SLE-affected human and murine lymphocytes. Reducing Fli-1 expression in MRL/lpr mice decreased antibody production, proteinuria, renal pathology, and mortality. Compared to those with...
| Veröffentlicht in: | Clinical immunology (Orlando, Fla.). - 1999. - 129(2008), 1 vom: 01. Okt., Seite 19-30 |
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| Weitere Verfasser: | , , , |
| Format: | Online-Aufsatz |
| Sprache: | English |
| Veröffentlicht: |
2008
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| Zugriff auf das übergeordnete Werk: | Clinical immunology (Orlando, Fla.) |
| Schlagworte: | Journal Article Fli1 protein, mouse Il12a protein, mouse Interleukin-12 Subunit p35 NFATC Transcription Factors Proto-Oncogene Protein c-fli-1 Receptors, Antigen, B-Cell Toll-Like Receptor 4 Toll-Like Receptor 9 |
| Zusammenfassung: | Transgenic overexpression of Fli-1 in normal mice leads to SLE-like disease and increased expression was reported in SLE-affected human and murine lymphocytes. Reducing Fli-1 expression in MRL/lpr mice decreased antibody production, proteinuria, renal pathology, and mortality. Compared to those with wild-type expression of Fli-1, we report here that proliferative responses of Fli-1-deficient naïve B cells to several mitogens were reduced in lupus-prone and control mice. Expression of mitogen receptors, including BCR, TLR4, and TLR9, was not significantly impacted in Fli-1-deficient naïve B cells. IL12a transcripts were upregulated and NFAT transcripts were downregulated in Fli-1-deficient MRL/lpr B cells. These results demonstrate that Fli-1 deficiency affects B cell proliferative responses to mitogens, independent of BCR and TLR expression. IL12a and NFAT, known to influence proliferation, were identified as potential mediators of this effect. This may be a mechanism by which overexpression of Fli-1 contributes to B cell hyperactivity and subsequent SLE pathogenesis |
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| Beschreibung: | Date Completed 07.10.2008 Date Revised 20.10.2021 published: Print-Electronic Citation Status MEDLINE |
| ISSN: | 1521-7035 |
| DOI: | 10.1016/j.clim.2008.05.010 |