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Lupus Susceptibility Gene Pbx1 Regulates STAT3 in T cells via JAK2/STAT3 Signaling Pathway
- Source :
- The Journal of Immunology. 208:103.01-103.01
- Publication Year :
- 2022
- Publisher :
- The American Association of Immunologists, 2022.
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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. U3A STAT3 reporter cells transfected with Pbx1-B plasmid have a greater luciferase expression, and hence pSTAT3 transcriptional activity in comparison to cells transfected with Pbx1-D or control plasmids. We also observed that Jurkat T cells stably overexpressing Pbx1-B increases STAT3 gene expression as compared to Pbx1-D. Furthermore, Pbx1 silencing in Jurkat T cells leads to the attenuation of STAT3 message. 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 (R01 AI045050) to LM.
- Subjects :
- Immunology
Immunology and Allergy
Subjects
Details
- ISSN :
- 15506606 and 00221767
- Volume :
- 208
- Database :
- OpenAIRE
- Journal :
- The Journal of Immunology
- Accession number :
- edsair.doi...........c9c4047e6ed23dc4c72a40fa43371bc5