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- W4313373314 abstract "Abstract Systemic Lupus Erythematosus (SLE) is an autoimmune disease in which poorly characterized genetic factors lead to the production of autoreactive or inflammatory T cells. Pre-B cell leukemia homeobox 1 (Pbx1) is a transcription factor whose dominant negative splice isoform (Pbx1-D) is overexpressed in CD4 T cells of lupus patients and lupus-prone mice as compared to the normal isoform (Pbx1-B). Pbx1-D overexpression impairs Treg cell development and function while favoring the production of follicular helper T cells. Based on previous studies showing that Pbx1 promotes cell proliferation via JAK2/STAT3 signaling pathway in a renal cell carcinoma, we hypothesized that Pbx1-D decreases T cell proliferation and viability by attenuating the JAK2/STAT3 signaling pathway. Pbx1-B or Pbx1-D expression plasmids increased pSTAT3 protein levels but there was no difference between the two isoforms in 293T cells. U3A STAT3 reporter cells transfected with Pbx1-B plasmid have greater luciferase expression, and hence pSTAT3 transcriptional activity in comparison to cells transfected with Pbx1-D or control plasmids. We also observed that Pbx1-B increases the expression of Jak2 and Stat3 message as compared to Pbx1-D. These results suggest a mechanism by which Pbx1 contributes to impaired T cells in lupus pathogenesis is via the JAK2/STAT3 pathway. Current studies are conducted to dissect the mechanism by which Pbx1 regulates this pathway in primary T cells. Supported by a grant from the NIH (RO1AI04505021) to LM" @default.
- W4313373314 created "2023-01-06" @default.
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- W4313373314 date "2020-05-01" @default.
- W4313373314 modified "2023-09-27" @default.
- W4313373314 title "Regulation of the JAK2/STAT3 Signaling Pathway by the Lupus Susceptibility Gene <i>Pbx1</i>" @default.
- W4313373314 doi "https://doi.org/10.4049/jimmunol.204.supp.80.7" @default.
- W4313373314 hasPublicationYear "2020" @default.
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